<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2025 Workiva-->
<!--r:f99d5d1e-d265-48a7-b1db-963f1d1d748c,g:843f577d-9aa5-4eaa-b927-61a4f7e0ce6c-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:roleRef roleURI="http://www.biocryst.com/role/ConsolidatedBalanceSheets" xlink:type="simple" xlink:href="bcrx-20241231.xsd#ConsolidatedBalanceSheets"/>
  <link:calculationLink xlink:role="http://www.biocryst.com/role/ConsolidatedBalanceSheets" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Assets_a5c73e88-e681-4d7a-8938-e703136ead45" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_Assets"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsNoncurrent_bb5015bc-4fef-44cd-b00b-5db0cf7ee0aa" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherAssetsNoncurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_a5c73e88-e681-4d7a-8938-e703136ead45" xlink:to="loc_us-gaap_OtherAssetsNoncurrent_bb5015bc-4fef-44cd-b00b-5db0cf7ee0aa" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermInvestments_f6f98c47-129b-433c-a568-4e596daa2373" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermInvestments"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_a5c73e88-e681-4d7a-8938-e703136ead45" xlink:to="loc_us-gaap_LongTermInvestments_f6f98c47-129b-433c-a568-4e596daa2373" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_36dcb017-56df-430c-b051-73d7e2519fc8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_a5c73e88-e681-4d7a-8938-e703136ead45" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentNet_36dcb017-56df-430c-b051-73d7e2519fc8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_2531f3be-cb49-49dd-8af6-fe0e4d58b66e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetsCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_a5c73e88-e681-4d7a-8938-e703136ead45" xlink:to="loc_us-gaap_AssetsCurrent_2531f3be-cb49-49dd-8af6-fe0e4d58b66e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryNoncurrent_cadc7809-465c-4b4e-a116-a7a8a3858daa" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryNoncurrent"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_a5c73e88-e681-4d7a-8938-e703136ead45" xlink:to="loc_us-gaap_InventoryNoncurrent_cadc7809-465c-4b4e-a116-a7a8a3858daa" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RightOfUseAssetsNoncurrent_4eed7846-57df-48ea-a79f-453b26c804a5" xlink:href="bcrx-20241231.xsd#bcrx_RightOfUseAssetsNoncurrent"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_a5c73e88-e681-4d7a-8938-e703136ead45" xlink:to="loc_bcrx_RightOfUseAssetsNoncurrent_4eed7846-57df-48ea-a79f-453b26c804a5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_d8a6b3d9-6fe5-4a34-81a7-27718d3b00e3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetsCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_44a4caab-e501-4cce-93fa-4687f1fd891e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_d8a6b3d9-6fe5-4a34-81a7-27718d3b00e3" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_44a4caab-e501-4cce-93fa-4687f1fd891e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_95ce40c7-be91-4506-89c0-98c767722f5b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_d8a6b3d9-6fe5-4a34-81a7-27718d3b00e3" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_95ce40c7-be91-4506-89c0-98c767722f5b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableNetCurrent_8387c422-f3b1-48d1-9fb3-808fa6eeb797" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccountsReceivableNetCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_d8a6b3d9-6fe5-4a34-81a7-27718d3b00e3" xlink:to="loc_us-gaap_AccountsReceivableNetCurrent_8387c422-f3b1-48d1-9fb3-808fa6eeb797" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrent_c85fba96-2123-48d6-9470-7aa2078a2199" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PrepaidExpenseAndOtherAssetsCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_d8a6b3d9-6fe5-4a34-81a7-27718d3b00e3" xlink:to="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrent_c85fba96-2123-48d6-9470-7aa2078a2199" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsAtCarryingValue_497272a0-5da2-400f-91d3-c031a5a6cf41" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedCashAndCashEquivalentsAtCarryingValue"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_d8a6b3d9-6fe5-4a34-81a7-27718d3b00e3" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsAtCarryingValue_497272a0-5da2-400f-91d3-c031a5a6cf41" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_InventoryCurrent_352cd0fd-d9c1-44d0-93cd-a579b20164a5" xlink:href="bcrx-20241231.xsd#bcrx_InventoryCurrent"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_d8a6b3d9-6fe5-4a34-81a7-27718d3b00e3" xlink:to="loc_bcrx_InventoryCurrent_352cd0fd-d9c1-44d0-93cd-a579b20164a5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_e4e698d9-e846-45d3-9b97-f07e25b47f0b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_Liabilities"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltyFinancingLiabilitiesNoncurrent_2216d69c-16a0-47eb-868f-19a7094a1d5f" xlink:href="bcrx-20241231.xsd#bcrx_RoyaltyFinancingLiabilitiesNoncurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_e4e698d9-e846-45d3-9b97-f07e25b47f0b" xlink:to="loc_bcrx_RoyaltyFinancingLiabilitiesNoncurrent_2216d69c-16a0-47eb-868f-19a7094a1d5f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_d28e8d02-db07-40f3-8018-b20ac89ea5c3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_e4e698d9-e846-45d3-9b97-f07e25b47f0b" xlink:to="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_d28e8d02-db07-40f3-8018-b20ac89ea5c3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_48295407-3e11-42be-89e4-b12f247dc4bc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_e4e698d9-e846-45d3-9b97-f07e25b47f0b" xlink:to="loc_us-gaap_LiabilitiesCurrent_48295407-3e11-42be-89e4-b12f247dc4bc" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtNoncurrent_bd8089a7-f8f7-4f59-ac01-18245b1e0557" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermDebtNoncurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_e4e698d9-e846-45d3-9b97-f07e25b47f0b" xlink:to="loc_us-gaap_LongTermDebtNoncurrent_bd8089a7-f8f7-4f59-ac01-18245b1e0557" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiabilityNoncurrent_3f2e2f0c-f430-4152-a364-75a2234f2556" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinanceLeaseLiabilityNoncurrent"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_e4e698d9-e846-45d3-9b97-f07e25b47f0b" xlink:to="loc_us-gaap_FinanceLeaseLiabilityNoncurrent_3f2e2f0c-f430-4152-a364-75a2234f2556" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesAndStockholdersEquity_7543c6a8-37ec-420c-864f-8bdd3f1556af" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesAndStockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_044c1005-b26d-44db-9cfa-7e3a6464c562" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockholdersEquity"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_7543c6a8-37ec-420c-864f-8bdd3f1556af" xlink:to="loc_us-gaap_StockholdersEquity_044c1005-b26d-44db-9cfa-7e3a6464c562" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_3d950177-de17-479c-931a-4b24b40b65bf" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_Liabilities"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_7543c6a8-37ec-420c-864f-8bdd3f1556af" xlink:to="loc_us-gaap_Liabilities_3d950177-de17-479c-931a-4b24b40b65bf" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_8b6cef1c-3075-43fe-90ff-c0e15aae8c34" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesCurrent_ac5af554-f823-4e46-b018-b4f2b3299b68" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccruedLiabilitiesCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_8b6cef1c-3075-43fe-90ff-c0e15aae8c34" xlink:to="loc_us-gaap_AccruedLiabilitiesCurrent_ac5af554-f823-4e46-b018-b4f2b3299b68" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsPayableCurrent_7f89d44f-4925-47bd-8ce8-0fd6f3bc8dbf" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccountsPayableCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_8b6cef1c-3075-43fe-90ff-c0e15aae8c34" xlink:to="loc_us-gaap_AccountsPayableCurrent_7f89d44f-4925-47bd-8ce8-0fd6f3bc8dbf" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltyFinancingLiabilitiesCurrent_291179bc-98e1-43d6-8ec8-3071c81ed7e9" xlink:href="bcrx-20241231.xsd#bcrx_RoyaltyFinancingLiabilitiesCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_8b6cef1c-3075-43fe-90ff-c0e15aae8c34" xlink:to="loc_bcrx_RoyaltyFinancingLiabilitiesCurrent_291179bc-98e1-43d6-8ec8-3071c81ed7e9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiabilityCurrent_8fef132f-c584-469b-bdcc-6e448eb1d0fd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinanceLeaseLiabilityCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_8b6cef1c-3075-43fe-90ff-c0e15aae8c34" xlink:to="loc_us-gaap_FinanceLeaseLiabilityCurrent_8fef132f-c584-469b-bdcc-6e448eb1d0fd" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityCurrent_3f7ad5e7-5f52-473b-9489-b8ba24a137a3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiabilityCurrent"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_8b6cef1c-3075-43fe-90ff-c0e15aae8c34" xlink:to="loc_us-gaap_OperatingLeaseLiabilityCurrent_3f7ad5e7-5f52-473b-9489-b8ba24a137a3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_f2ba3a09-cd99-4aca-9731-383b0d6ba963" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsAccumulatedDeficit_0aed598f-f4dd-4fec-ba40-010e78f5b7d2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RetainedEarningsAccumulatedDeficit"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_f2ba3a09-cd99-4aca-9731-383b0d6ba963" xlink:to="loc_us-gaap_RetainedEarningsAccumulatedDeficit_0aed598f-f4dd-4fec-ba40-010e78f5b7d2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_df252221-c459-405c-8cca-4cffffb80805" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_f2ba3a09-cd99-4aca-9731-383b0d6ba963" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_df252221-c459-405c-8cca-4cffffb80805" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapital_e39ca70f-340b-4256-9cb1-ec9ebd4802a1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AdditionalPaidInCapital"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_f2ba3a09-cd99-4aca-9731-383b0d6ba963" xlink:to="loc_us-gaap_AdditionalPaidInCapital_e39ca70f-340b-4256-9cb1-ec9ebd4802a1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockValue_fec693db-6ef1-4ade-8599-ddd22b348b64" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PreferredStockValue"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_f2ba3a09-cd99-4aca-9731-383b0d6ba963" xlink:to="loc_us-gaap_PreferredStockValue_fec693db-6ef1-4ade-8599-ddd22b348b64" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockValue_ad10a152-390f-4db6-bc7a-7d450f957c5e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockValue"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_f2ba3a09-cd99-4aca-9731-383b0d6ba963" xlink:to="loc_us-gaap_CommonStockValue_ad10a152-390f-4db6-bc7a-7d450f957c5e" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/ConsolidatedStatementsofComprehensiveLoss" xlink:type="simple" xlink:href="bcrx-20241231.xsd#ConsolidatedStatementsofComprehensiveLoss"/>
  <link:calculationLink xlink:role="http://www.biocryst.com/role/ConsolidatedStatementsofComprehensiveLoss" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_OtherComprehensiveIncomeLossBeforeReclassificationsNetOfAdjustmentsNetOfTaxPortionAttributableToParent_5256fed9-3959-4800-9a5e-fd7a3cfd7edf" xlink:href="bcrx-20241231.xsd#bcrx_OtherComprehensiveIncomeLossBeforeReclassificationsNetOfAdjustmentsNetOfTaxPortionAttributableToParent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_84c615f4-c402-4abe-962b-22d7fee2eefb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_bcrx_OtherComprehensiveIncomeLossBeforeReclassificationsNetOfAdjustmentsNetOfTaxPortionAttributableToParent_5256fed9-3959-4800-9a5e-fd7a3cfd7edf" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_84c615f4-c402-4abe-962b-22d7fee2eefb" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationAdjustmentNetOfTaxPortionAttributableToParent_cc621cb7-b6cb-4fb5-af5b-57a7ad7282ea" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationAdjustmentNetOfTaxPortionAttributableToParent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_bcrx_OtherComprehensiveIncomeLossBeforeReclassificationsNetOfAdjustmentsNetOfTaxPortionAttributableToParent_5256fed9-3959-4800-9a5e-fd7a3cfd7edf" xlink:to="loc_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationAdjustmentNetOfTaxPortionAttributableToParent_cc621cb7-b6cb-4fb5-af5b-57a7ad7282ea" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_9c3a94ac-b3f5-413c-9906-3c60fc4c9f34" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_431fba67-e015-4873-85b0-15e05c83552a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_9c3a94ac-b3f5-413c-9906-3c60fc4c9f34" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_431fba67-e015-4873-85b0-15e05c83552a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_c4576548-6e79-4be5-a5d6-e53c2c9cb3ea" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_9c3a94ac-b3f5-413c-9906-3c60fc4c9f34" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_c4576548-6e79-4be5-a5d6-e53c2c9cb3ea" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_782d1e1d-a3c6-4f30-8bab-9849c0f5602d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_bdf5910b-b075-4d3d-8912-cffdb226f97e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss_782d1e1d-a3c6-4f30-8bab-9849c0f5602d" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_bdf5910b-b075-4d3d-8912-cffdb226f97e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpenses_30032ff3-19df-4ae4-908d-c54d8d533015" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostsAndExpenses"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss_782d1e1d-a3c6-4f30-8bab-9849c0f5602d" xlink:to="loc_us-gaap_CostsAndExpenses_30032ff3-19df-4ae4-908d-c54d8d533015" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpenses_ff3ab90e-2f50-4820-9a1f-5c6010d48c1d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostsAndExpenses"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_Royalty_d8f608b4-86d4-4072-932b-ce84ae6c1f54" xlink:href="bcrx-20241231.xsd#bcrx_Royalty"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CostsAndExpenses_ff3ab90e-2f50-4820-9a1f-5c6010d48c1d" xlink:to="loc_bcrx_Royalty_d8f608b4-86d4-4072-932b-ce84ae6c1f54" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingGeneralAndAdministrativeExpense_43990251-2332-4cac-984b-90c0c8ba6800" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SellingGeneralAndAdministrativeExpense"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CostsAndExpenses_ff3ab90e-2f50-4820-9a1f-5c6010d48c1d" xlink:to="loc_us-gaap_SellingGeneralAndAdministrativeExpense_43990251-2332-4cac-984b-90c0c8ba6800" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_4196c265-a95a-467f-b8ce-072e18a5dad8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CostsAndExpenses_ff3ab90e-2f50-4820-9a1f-5c6010d48c1d" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_4196c265-a95a-467f-b8ce-072e18a5dad8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSold_8262f4a8-a7c5-49f7-b778-98d433dd5859" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostOfGoodsAndServicesSold"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CostsAndExpenses_ff3ab90e-2f50-4820-9a1f-5c6010d48c1d" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSold_8262f4a8-a7c5-49f7-b778-98d433dd5859" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NonoperatingIncomeExpense_a0e066d8-703a-4b5e-a172-a7e9d43bd563" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NonoperatingIncomeExpense"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainsLossesOnExtinguishmentOfDebt_49756afb-23c9-4839-8ef0-e78e9e166c80" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_GainsLossesOnExtinguishmentOfDebt"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NonoperatingIncomeExpense_a0e066d8-703a-4b5e-a172-a7e9d43bd563" xlink:to="loc_us-gaap_GainsLossesOnExtinguishmentOfDebt_49756afb-23c9-4839-8ef0-e78e9e166c80" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainLossOnForeignCurrencyDerivativeInstrumentsNotDesignatedAsHedgingInstruments_a2968286-01b4-45d8-a876-95d915da0640" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_GainLossOnForeignCurrencyDerivativeInstrumentsNotDesignatedAsHedgingInstruments"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NonoperatingIncomeExpense_a0e066d8-703a-4b5e-a172-a7e9d43bd563" xlink:to="loc_us-gaap_GainLossOnForeignCurrencyDerivativeInstrumentsNotDesignatedAsHedgingInstruments_a2968286-01b4-45d8-a876-95d915da0640" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseNonoperating_ce6d1040-0cfd-44e9-a04b-389e6ada46f1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InterestExpenseNonoperating"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NonoperatingIncomeExpense_a0e066d8-703a-4b5e-a172-a7e9d43bd563" xlink:to="loc_us-gaap_InterestExpenseNonoperating_ce6d1040-0cfd-44e9-a04b-389e6ada46f1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestAndOtherIncome_347338a6-6dcf-4949-9690-f313f04d0917" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InterestAndOtherIncome"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NonoperatingIncomeExpense_a0e066d8-703a-4b5e-a172-a7e9d43bd563" xlink:to="loc_us-gaap_InterestAndOtherIncome_347338a6-6dcf-4949-9690-f313f04d0917" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComprehensiveIncomeNetOfTax_522d6b36-da3b-4477-9106-a351e3e0d649" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ComprehensiveIncomeNetOfTax"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_OtherComprehensiveIncomeLossBeforeReclassificationsNetOfAdjustmentsNetOfTaxPortionAttributableToParent_729494d0-875c-4893-b30e-462873215f11" xlink:href="bcrx-20241231.xsd#bcrx_OtherComprehensiveIncomeLossBeforeReclassificationsNetOfAdjustmentsNetOfTaxPortionAttributableToParent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_522d6b36-da3b-4477-9106-a351e3e0d649" xlink:to="loc_bcrx_OtherComprehensiveIncomeLossBeforeReclassificationsNetOfAdjustmentsNetOfTaxPortionAttributableToParent_729494d0-875c-4893-b30e-462873215f11" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_b1cf8958-e4ed-423c-bcff-683466ddb00d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_522d6b36-da3b-4477-9106-a351e3e0d649" xlink:to="loc_us-gaap_NetIncomeLoss_b1cf8958-e4ed-423c-bcff-683466ddb00d" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/ConsolidatedStatementsofCashFlows" xlink:type="simple" xlink:href="bcrx-20241231.xsd#ConsolidatedStatementsofCashFlows"/>
  <link:calculationLink xlink:role="http://www.biocryst.com/role/ConsolidatedStatementsofCashFlows" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_94b900bb-1961-4cfe-9242-b1c78c5549d6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_387b4da6-5577-4784-a2ce-dff39cd1a0e6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_94b900bb-1961-4cfe-9242-b1c78c5549d6" xlink:to="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_387b4da6-5577-4784-a2ce-dff39cd1a0e6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_f94c3a3f-fcc6-4d6d-b72c-0beb2fdfd901" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_94b900bb-1961-4cfe-9242-b1c78c5549d6" xlink:to="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_f94c3a3f-fcc6-4d6d-b72c-0beb2fdfd901" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_06d7f1eb-87bf-4bfa-8def-8da9657ad85d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_94b900bb-1961-4cfe-9242-b1c78c5549d6" xlink:to="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_06d7f1eb-87bf-4bfa-8def-8da9657ad85d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_b64911b7-2268-4b1e-9c23-d7a32eea4926" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_94b900bb-1961-4cfe-9242-b1c78c5549d6" xlink:to="loc_us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_b64911b7-2268-4b1e-9c23-d7a32eea4926" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_cc8dcd99-cd5b-490f-8ce6-9b5c994cb7c4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccountsPayable_4eb7863b-f086-452b-b02c-fe93a66ee4c1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInAccountsPayable"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_cc8dcd99-cd5b-490f-8ce6-9b5c994cb7c4" xlink:to="loc_us-gaap_IncreaseDecreaseInAccountsPayable_4eb7863b-f086-452b-b02c-fe93a66ee4c1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInContractWithCustomerLiability_752ee8fd-a0e2-4ddc-be52-685e1f64fbe2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInContractWithCustomerLiability"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_cc8dcd99-cd5b-490f-8ce6-9b5c994cb7c4" xlink:to="loc_us-gaap_IncreaseDecreaseInContractWithCustomerLiability_752ee8fd-a0e2-4ddc-be52-685e1f64fbe2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_b35a400b-e18c-4825-ad19-cc1005418c55" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_cc8dcd99-cd5b-490f-8ce6-9b5c994cb7c4" xlink:to="loc_us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_b35a400b-e18c-4825-ad19-cc1005418c55" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_NonCashInterestExpenseOnRoyaltyFinancingLiabilitiesAndSecuredTermLoanAndAmortizationOfDebtIssuanceCosts_35eb19da-8b8f-4108-8ff8-b7478491a9f1" xlink:href="bcrx-20241231.xsd#bcrx_NonCashInterestExpenseOnRoyaltyFinancingLiabilitiesAndSecuredTermLoanAndAmortizationOfDebtIssuanceCosts"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_cc8dcd99-cd5b-490f-8ce6-9b5c994cb7c4" xlink:to="loc_bcrx_NonCashInterestExpenseOnRoyaltyFinancingLiabilitiesAndSecuredTermLoanAndAmortizationOfDebtIssuanceCosts_35eb19da-8b8f-4108-8ff8-b7478491a9f1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInReceivables_02f91f43-aae6-41ef-abaa-f95fd520dbee" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInReceivables"/>
    <link:calculationArc order="5" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_cc8dcd99-cd5b-490f-8ce6-9b5c994cb7c4" xlink:to="loc_us-gaap_IncreaseDecreaseInReceivables_02f91f43-aae6-41ef-abaa-f95fd520dbee" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_80a3d3fb-84eb-4567-8051-c3bc5900a411" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_cc8dcd99-cd5b-490f-8ce6-9b5c994cb7c4" xlink:to="loc_us-gaap_NetIncomeLoss_80a3d3fb-84eb-4567-8051-c3bc5900a411" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInInventories_f75e7317-a1e0-4864-b557-fbe2b22488a6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInInventories"/>
    <link:calculationArc order="7" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_cc8dcd99-cd5b-490f-8ce6-9b5c994cb7c4" xlink:to="loc_us-gaap_IncreaseDecreaseInInventories_f75e7317-a1e0-4864-b557-fbe2b22488a6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainsLossesOnExtinguishmentOfDebt_09a92a6b-5725-4f9c-ab0c-dd7421a66521" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_GainsLossesOnExtinguishmentOfDebt"/>
    <link:calculationArc order="8" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_cc8dcd99-cd5b-490f-8ce6-9b5c994cb7c4" xlink:to="loc_us-gaap_GainsLossesOnExtinguishmentOfDebt_09a92a6b-5725-4f9c-ab0c-dd7421a66521" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DepreciationDepletionAndAmortization_c350a879-1a7b-44f1-8a7f-d28f7d735a7c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DepreciationDepletionAndAmortization"/>
    <link:calculationArc order="9" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_cc8dcd99-cd5b-490f-8ce6-9b5c994cb7c4" xlink:to="loc_us-gaap_DepreciationDepletionAndAmortization_c350a879-1a7b-44f1-8a7f-d28f7d735a7c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensation_aa4cba34-ccaf-431b-9939-82978ddeda94" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensation"/>
    <link:calculationArc order="10" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_cc8dcd99-cd5b-490f-8ce6-9b5c994cb7c4" xlink:to="loc_us-gaap_ShareBasedCompensation_aa4cba34-ccaf-431b-9939-82978ddeda94" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AmortizationOfPremiumDiscountOnInvestments_8db85901-658a-47d2-a194-17129d7e6dce" xlink:href="bcrx-20241231.xsd#bcrx_AmortizationOfPremiumDiscountOnInvestments"/>
    <link:calculationArc order="11" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_cc8dcd99-cd5b-490f-8ce6-9b5c994cb7c4" xlink:to="loc_bcrx_AmortizationOfPremiumDiscountOnInvestments_8db85901-658a-47d2-a194-17129d7e6dce" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryWriteDown_76b9982b-873c-440b-8c0d-5bfbd3068d9a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryWriteDown"/>
    <link:calculationArc order="12" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_cc8dcd99-cd5b-490f-8ce6-9b5c994cb7c4" xlink:to="loc_us-gaap_InventoryWriteDown_76b9982b-873c-440b-8c0d-5bfbd3068d9a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TangibleAssetImpairmentCharges_42ea4b57-83a9-4f52-b311-3a30c6b531e7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TangibleAssetImpairmentCharges"/>
    <link:calculationArc order="13" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_cc8dcd99-cd5b-490f-8ce6-9b5c994cb7c4" xlink:to="loc_us-gaap_TangibleAssetImpairmentCharges_42ea4b57-83a9-4f52-b311-3a30c6b531e7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_f3cf7052-4f5b-459a-b6a5-ad67d60ab864" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepaymentsOfSecuredDebt_d47443a7-ee51-4899-ae6a-33d0387ecb9e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RepaymentsOfSecuredDebt"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_f3cf7052-4f5b-459a-b6a5-ad67d60ab864" xlink:to="loc_us-gaap_RepaymentsOfSecuredDebt_d47443a7-ee51-4899-ae6a-33d0387ecb9e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsOfDebtIssuanceCosts_82d0418e-1d84-479f-906d-3337378b0b6a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentsOfDebtIssuanceCosts"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_f3cf7052-4f5b-459a-b6a5-ad67d60ab864" xlink:to="loc_us-gaap_PaymentsOfDebtIssuanceCosts_82d0418e-1d84-479f-906d-3337378b0b6a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfLongTermDebt_6757cc48-c0df-43ad-8b65-ba798a2f9160" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromIssuanceOfLongTermDebt"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_f3cf7052-4f5b-459a-b6a5-ad67d60ab864" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfLongTermDebt_6757cc48-c0df-43ad-8b65-ba798a2f9160" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsOfLoanCosts_1f134765-68b9-4f09-a1eb-df90ffbe02ea" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentsOfLoanCosts"/>
    <link:calculationArc order="4" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_f3cf7052-4f5b-459a-b6a5-ad67d60ab864" xlink:to="loc_us-gaap_PaymentsOfLoanCosts_1f134765-68b9-4f09-a1eb-df90ffbe02ea" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_efc7db50-2c40-4f6c-9a18-e41023a74198" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation"/>
    <link:calculationArc order="5" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_f3cf7052-4f5b-459a-b6a5-ad67d60ab864" xlink:to="loc_us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_efc7db50-2c40-4f6c-9a18-e41023a74198" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_ProceedsFromIssuanceOfCommonStockIssuedForServices_85567a49-cfca-4732-93fe-ae21f52625ef" xlink:href="bcrx-20241231.xsd#bcrx_ProceedsFromIssuanceOfCommonStockIssuedForServices"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_f3cf7052-4f5b-459a-b6a5-ad67d60ab864" xlink:to="loc_bcrx_ProceedsFromIssuanceOfCommonStockIssuedForServices_85567a49-cfca-4732-93fe-ae21f52625ef" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeasePrincipalPayments_16f05e4b-1073-4627-a462-1446179b79c1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinanceLeasePrincipalPayments"/>
    <link:calculationArc order="7" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_f3cf7052-4f5b-459a-b6a5-ad67d60ab864" xlink:to="loc_us-gaap_FinanceLeasePrincipalPayments_16f05e4b-1073-4627-a462-1446179b79c1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_c5708e1c-1360-48fc-bc4b-b97bef31479b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions"/>
    <link:calculationArc order="8" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_f3cf7052-4f5b-459a-b6a5-ad67d60ab864" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_c5708e1c-1360-48fc-bc4b-b97bef31479b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations_11522727-e932-459a-a4b3-4e5baf01a0ad" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RestrictedCashAndCashEquivalentsIncludedInOtherAssetsNonCurrent_05fa045b-cf46-4d36-8aff-0837f790d7fe" xlink:href="bcrx-20241231.xsd#bcrx_RestrictedCashAndCashEquivalentsIncludedInOtherAssetsNonCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations_11522727-e932-459a-a4b3-4e5baf01a0ad" xlink:to="loc_bcrx_RestrictedCashAndCashEquivalentsIncludedInOtherAssetsNonCurrent_05fa045b-cf46-4d36-8aff-0837f790d7fe" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsAtCarryingValue_4a330e09-ce1a-4c34-9bc9-4526a7a1f97d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedCashAndCashEquivalentsAtCarryingValue"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations_11522727-e932-459a-a4b3-4e5baf01a0ad" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsAtCarryingValue_4a330e09-ce1a-4c34-9bc9-4526a7a1f97d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_6aa0b88d-2596-483c-bdc0-56f3a9c6a67d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations_11522727-e932-459a-a4b3-4e5baf01a0ad" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_6aa0b88d-2596-483c-bdc0-56f3a9c6a67d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_d6fcfc6f-585f-4a8e-82ff-5eeccad30462" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_cee899f2-129e-4d2a-9786-702616dd1a14" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_d6fcfc6f-585f-4a8e-82ff-5eeccad30462" xlink:to="loc_us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_cee899f2-129e-4d2a-9786-702616dd1a14" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_6ebe2480-435b-42e1-b034-e748486ea483" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_d6fcfc6f-585f-4a8e-82ff-5eeccad30462" xlink:to="loc_us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_6ebe2480-435b-42e1-b034-e748486ea483" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireProductiveAssets_a3f4a26c-b8aa-44eb-9b59-b5c7a83d723d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentsToAcquireProductiveAssets"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_d6fcfc6f-585f-4a8e-82ff-5eeccad30462" xlink:to="loc_us-gaap_PaymentsToAcquireProductiveAssets_a3f4a26c-b8aa-44eb-9b59-b5c7a83d723d" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/InvestmentScheduleofMaturityofInvestmentsDetails" xlink:type="simple" xlink:href="bcrx-20241231.xsd#InvestmentScheduleofMaturityofInvestmentsDetails"/>
  <link:calculationLink xlink:role="http://www.biocryst.com/role/InvestmentScheduleofMaturityofInvestmentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_90fc8575-f9c5-4dc2-a060-f1d729e3a4d3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_MaturingAfterOneYearThroughTwoYears_2895411f-0563-448d-aa23-d6c8135487ed" xlink:href="bcrx-20241231.xsd#bcrx_MaturingAfterOneYearThroughTwoYears"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_90fc8575-f9c5-4dc2-a060-f1d729e3a4d3" xlink:to="loc_bcrx_MaturingAfterOneYearThroughTwoYears_2895411f-0563-448d-aa23-d6c8135487ed" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearFairValue_554b011a-d221-4a0e-8749-5cccecc0bc37" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearFairValue"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_90fc8575-f9c5-4dc2-a060-f1d729e3a4d3" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearFairValue_554b011a-d221-4a0e-8749-5cccecc0bc37" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/InventorySummaryofInventoriesDetails" xlink:type="simple" xlink:href="bcrx-20241231.xsd#InventorySummaryofInventoriesDetails"/>
  <link:calculationLink xlink:role="http://www.biocryst.com/role/InventorySummaryofInventoriesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryGross_975a7739-9498-4d4d-85d6-25ef0542298a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryGross"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryRawMaterials_e99d855e-7add-4f46-b755-5bda1afa96b2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryRawMaterials"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryGross_975a7739-9498-4d4d-85d6-25ef0542298a" xlink:to="loc_us-gaap_InventoryRawMaterials_e99d855e-7add-4f46-b755-5bda1afa96b2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryFinishedGoods_cb50bf53-0b6e-49d7-af64-52e2c6c8adc2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryFinishedGoods"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryGross_975a7739-9498-4d4d-85d6-25ef0542298a" xlink:to="loc_us-gaap_InventoryFinishedGoods_cb50bf53-0b6e-49d7-af64-52e2c6c8adc2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryWorkInProcess_925acef0-e198-46c8-ad59-c1114e2e75d2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryWorkInProcess"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryGross_975a7739-9498-4d4d-85d6-25ef0542298a" xlink:to="loc_us-gaap_InventoryWorkInProcess_925acef0-e198-46c8-ad59-c1114e2e75d2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryNet_3a8766b2-8db2-4ae3-aa16-f6f67a4b978a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryNet"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryValuationReserves_e06bd431-ede0-4552-a314-b731ec2b136e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryValuationReserves"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryNet_3a8766b2-8db2-4ae3-aa16-f6f67a4b978a" xlink:to="loc_us-gaap_InventoryValuationReserves_e06bd431-ede0-4552-a314-b731ec2b136e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryGross_b1d279ee-8977-4b44-b23c-71e33b31f111" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InventoryGross"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_InventoryNet_3a8766b2-8db2-4ae3-aa16-f6f67a4b978a" xlink:to="loc_us-gaap_InventoryGross_b1d279ee-8977-4b44-b23c-71e33b31f111" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/PropertyandEquipmentPropertyandEquipmentDetails" xlink:type="simple" xlink:href="bcrx-20241231.xsd#PropertyandEquipmentPropertyandEquipmentDetails"/>
  <link:calculationLink xlink:role="http://www.biocryst.com/role/PropertyandEquipmentPropertyandEquipmentDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_2df5aa0a-79d2-4190-98cb-5801213c7044" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_3936c6ae-7c0c-4492-bc63-f8c27695b447" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentNet_2df5aa0a-79d2-4190-98cb-5801213c7044" xlink:to="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_3936c6ae-7c0c-4492-bc63-f8c27695b447" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentGross_0bb941c8-39f9-4996-baed-76f765355a6c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentGross"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentNet_2df5aa0a-79d2-4190-98cb-5801213c7044" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentGross_0bb941c8-39f9-4996-baed-76f765355a6c" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/AccruedExpensesAccruedExpensesDetails" xlink:type="simple" xlink:href="bcrx-20241231.xsd#AccruedExpensesAccruedExpensesDetails"/>
  <link:calculationLink xlink:role="http://www.biocryst.com/role/AccruedExpensesAccruedExpensesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesCurrent_50c822bc-9d65-4635-87d3-f19896c941fc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccruedLiabilitiesCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeRelatedLiabilitiesCurrent_efcfe2b3-26ac-4036-8514-341765be095a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeRelatedLiabilitiesCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrent_50c822bc-9d65-4635-87d3-f19896c941fc" xlink:to="loc_us-gaap_EmployeeRelatedLiabilitiesCurrent_efcfe2b3-26ac-4036-8514-341765be095a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RevenueRelatedReservesForDiscountsAndAllowances_3432dfc7-d076-4118-ba2f-b6047b4cbfd7" xlink:href="bcrx-20241231.xsd#bcrx_RevenueRelatedReservesForDiscountsAndAllowances"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrent_50c822bc-9d65-4635-87d3-f19896c941fc" xlink:to="loc_bcrx_RevenueRelatedReservesForDiscountsAndAllowances_3432dfc7-d076-4118-ba2f-b6047b4cbfd7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltiesPayable_1a2cb31b-b427-46ef-9344-63d881efa52c" xlink:href="bcrx-20241231.xsd#bcrx_RoyaltiesPayable"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrent_50c822bc-9d65-4635-87d3-f19896c941fc" xlink:to="loc_bcrx_RoyaltiesPayable_1a2cb31b-b427-46ef-9344-63d881efa52c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AccruedDevelopmentCosts_7d7a4e9b-e2f9-43ae-8f8d-de90bb791fb6" xlink:href="bcrx-20241231.xsd#bcrx_AccruedDevelopmentCosts"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrent_50c822bc-9d65-4635-87d3-f19896c941fc" xlink:to="loc_bcrx_AccruedDevelopmentCosts_7d7a4e9b-e2f9-43ae-8f8d-de90bb791fb6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAccruedLiabilitiesCurrent_e1ed058c-29c8-4b54-867f-864d428a09b8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherAccruedLiabilitiesCurrent"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrent_50c822bc-9d65-4635-87d3-f19896c941fc" xlink:to="loc_us-gaap_OtherAccruedLiabilitiesCurrent_e1ed058c-29c8-4b54-867f-864d428a09b8" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/LeaseObligationsAggregateLeaseExpenseUnderOperatingLeasesDetails" xlink:type="simple" xlink:href="bcrx-20241231.xsd#LeaseObligationsAggregateLeaseExpenseUnderOperatingLeasesDetails"/>
  <link:calculationLink xlink:role="http://www.biocryst.com/role/LeaseObligationsAggregateLeaseExpenseUnderOperatingLeasesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_FinancingLeaseExpense_c31e5b34-4445-4bbc-9170-a01e33e2e309" xlink:href="bcrx-20241231.xsd#bcrx_FinancingLeaseExpense"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseRightOfUseAssetAmortization_b6cdee5e-9122-436c-96e5-56dca49f4047" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinanceLeaseRightOfUseAssetAmortization"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_bcrx_FinancingLeaseExpense_c31e5b34-4445-4bbc-9170-a01e33e2e309" xlink:to="loc_us-gaap_FinanceLeaseRightOfUseAssetAmortization_b6cdee5e-9122-436c-96e5-56dca49f4047" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseInterestExpense_7d29cee8-e0d6-4fa2-a371-f97a245d7f21" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinanceLeaseInterestExpense"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_bcrx_FinancingLeaseExpense_c31e5b34-4445-4bbc-9170-a01e33e2e309" xlink:to="loc_us-gaap_FinanceLeaseInterestExpense_7d29cee8-e0d6-4fa2-a371-f97a245d7f21" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/LeaseObligationsBalanceSheetsoftheCompanysOperatingLeasesDetails" xlink:type="simple" xlink:href="bcrx-20241231.xsd#LeaseObligationsBalanceSheetsoftheCompanysOperatingLeasesDetails"/>
  <link:calculationLink xlink:role="http://www.biocryst.com/role/LeaseObligationsBalanceSheetsoftheCompanysOperatingLeasesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiability_ac0a175a-4153-4295-8772-f58aae8cb5f8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiability"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_081e9811-31f9-4243-9e7c-4b21009e0c2b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingLeaseLiability_ac0a175a-4153-4295-8772-f58aae8cb5f8" xlink:to="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_081e9811-31f9-4243-9e7c-4b21009e0c2b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityCurrent_623a6d95-94f4-4bcc-a3c7-426f8375b965" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiabilityCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingLeaseLiability_ac0a175a-4153-4295-8772-f58aae8cb5f8" xlink:to="loc_us-gaap_OperatingLeaseLiabilityCurrent_623a6d95-94f4-4bcc-a3c7-426f8375b965" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/LeaseObligationsBalanceSheetsoftheCompanysFinanceLeasesDetails" xlink:type="simple" xlink:href="bcrx-20241231.xsd#LeaseObligationsBalanceSheetsoftheCompanysFinanceLeasesDetails"/>
  <link:calculationLink xlink:role="http://www.biocryst.com/role/LeaseObligationsBalanceSheetsoftheCompanysFinanceLeasesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiability_0b8f21c8-c099-4321-ba5d-9ec9ba4a4591" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinanceLeaseLiability"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiabilityCurrent_770669a6-15f0-4826-ab41-385388b99234" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinanceLeaseLiabilityCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_FinanceLeaseLiability_0b8f21c8-c099-4321-ba5d-9ec9ba4a4591" xlink:to="loc_us-gaap_FinanceLeaseLiabilityCurrent_770669a6-15f0-4826-ab41-385388b99234" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiabilityNoncurrent_fcd0cc33-8dc6-43c8-b188-a6839b411d8b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinanceLeaseLiabilityNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_FinanceLeaseLiability_0b8f21c8-c099-4321-ba5d-9ec9ba4a4591" xlink:to="loc_us-gaap_FinanceLeaseLiabilityNoncurrent_fcd0cc33-8dc6-43c8-b188-a6839b411d8b" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/LeaseObligationsMaturitiesofOperatingLeaseLiabilitiesDetails" xlink:type="simple" xlink:href="bcrx-20241231.xsd#LeaseObligationsMaturitiesofOperatingLeaseLiabilitiesDetails"/>
  <link:calculationLink xlink:role="http://www.biocryst.com/role/LeaseObligationsMaturitiesofOperatingLeaseLiabilitiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_5558fd3e-7c5e-4ee2-929a-eb4cff243f57" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiability_dd1b71a5-8897-4c79-8c99-97dadcd8085b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiability"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_5558fd3e-7c5e-4ee2-929a-eb4cff243f57" xlink:to="loc_us-gaap_OperatingLeaseLiability_dd1b71a5-8897-4c79-8c99-97dadcd8085b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_697cb52b-af72-4a82-be1e-f5e77298eb80" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_5558fd3e-7c5e-4ee2-929a-eb4cff243f57" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_697cb52b-af72-4a82-be1e-f5e77298eb80" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiabilityPaymentsDue_edcd7a21-d201-44f3-a1b0-03e5e14c38a2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinanceLeaseLiabilityPaymentsDue"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiabilityPaymentsDueNextTwelveMonths_61f7c553-28a6-4494-babb-7183ed7765d6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinanceLeaseLiabilityPaymentsDueNextTwelveMonths"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_FinanceLeaseLiabilityPaymentsDue_edcd7a21-d201-44f3-a1b0-03e5e14c38a2" xlink:to="loc_us-gaap_FinanceLeaseLiabilityPaymentsDueNextTwelveMonths_61f7c553-28a6-4494-babb-7183ed7765d6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiabilityPaymentsDueYearTwo_5d5c7c1a-3374-4017-b156-7a05d120c56c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinanceLeaseLiabilityPaymentsDueYearTwo"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_FinanceLeaseLiabilityPaymentsDue_edcd7a21-d201-44f3-a1b0-03e5e14c38a2" xlink:to="loc_us-gaap_FinanceLeaseLiabilityPaymentsDueYearTwo_5d5c7c1a-3374-4017-b156-7a05d120c56c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiabilityPaymentsDueYearThree_aa989819-cf73-46da-87e6-1f919fee6208" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinanceLeaseLiabilityPaymentsDueYearThree"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_FinanceLeaseLiabilityPaymentsDue_edcd7a21-d201-44f3-a1b0-03e5e14c38a2" xlink:to="loc_us-gaap_FinanceLeaseLiabilityPaymentsDueYearThree_aa989819-cf73-46da-87e6-1f919fee6208" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiabilityPaymentsDueYearFour_baccd745-42c5-4839-a26f-394308ced8a2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinanceLeaseLiabilityPaymentsDueYearFour"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_FinanceLeaseLiabilityPaymentsDue_edcd7a21-d201-44f3-a1b0-03e5e14c38a2" xlink:to="loc_us-gaap_FinanceLeaseLiabilityPaymentsDueYearFour_baccd745-42c5-4839-a26f-394308ced8a2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiabilityPaymentsDueYearFive_d404f7c5-dbe4-42cd-8644-8c6dbfa81393" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinanceLeaseLiabilityPaymentsDueYearFive"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_FinanceLeaseLiabilityPaymentsDue_edcd7a21-d201-44f3-a1b0-03e5e14c38a2" xlink:to="loc_us-gaap_FinanceLeaseLiabilityPaymentsDueYearFive_d404f7c5-dbe4-42cd-8644-8c6dbfa81393" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiabilityPaymentsDueAfterYearFive_7d7dc35c-517c-40c5-a420-d2e82bbea8ac" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinanceLeaseLiabilityPaymentsDueAfterYearFive"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_FinanceLeaseLiabilityPaymentsDue_edcd7a21-d201-44f3-a1b0-03e5e14c38a2" xlink:to="loc_us-gaap_FinanceLeaseLiabilityPaymentsDueAfterYearFive_7d7dc35c-517c-40c5-a420-d2e82bbea8ac" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/LeaseObligationsMaturitiesofOperatingLeaseLiabilitiesDetails_1" xlink:type="simple" xlink:href="bcrx-20241231.xsd#LeaseObligationsMaturitiesofOperatingLeaseLiabilitiesDetails_1"/>
  <link:calculationLink xlink:role="http://www.biocryst.com/role/LeaseObligationsMaturitiesofOperatingLeaseLiabilitiesDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiabilityPaymentsDue_9e850ac8-236b-4d63-b3b0-1d8133819fec" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinanceLeaseLiabilityPaymentsDue"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiabilityUndiscountedExcessAmount_301e9079-3847-4e4d-b849-2d2c33da7e8b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinanceLeaseLiabilityUndiscountedExcessAmount"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_FinanceLeaseLiabilityPaymentsDue_9e850ac8-236b-4d63-b3b0-1d8133819fec" xlink:to="loc_us-gaap_FinanceLeaseLiabilityUndiscountedExcessAmount_301e9079-3847-4e4d-b849-2d2c33da7e8b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiability_94f3687b-7a6b-45c2-9df1-5b036ca57bc2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinanceLeaseLiability"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_FinanceLeaseLiabilityPaymentsDue_9e850ac8-236b-4d63-b3b0-1d8133819fec" xlink:to="loc_us-gaap_FinanceLeaseLiability_94f3687b-7a6b-45c2-9df1-5b036ca57bc2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_831fbb7e-6f2b-41ba-a272-9b3b289ef1ee" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_8883e37f-5aaa-4c04-b332-ee68f78bcbc5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_831fbb7e-6f2b-41ba-a272-9b3b289ef1ee" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_8883e37f-5aaa-4c04-b332-ee68f78bcbc5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_6680b610-83e3-47f1-8594-c1be398a00a7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_831fbb7e-6f2b-41ba-a272-9b3b289ef1ee" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_6680b610-83e3-47f1-8594-c1be398a00a7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_f83529d5-163f-48fe-952f-9e9523f9cf0f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_831fbb7e-6f2b-41ba-a272-9b3b289ef1ee" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_f83529d5-163f-48fe-952f-9e9523f9cf0f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_e2649000-8a0f-4218-ba83-b3ae1e2f8981" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_831fbb7e-6f2b-41ba-a272-9b3b289ef1ee" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_e2649000-8a0f-4218-ba83-b3ae1e2f8981" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_eb3915c4-8f0d-4424-a564-8a2d43794fb3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_831fbb7e-6f2b-41ba-a272-9b3b289ef1ee" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_eb3915c4-8f0d-4424-a564-8a2d43794fb3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_31632e83-eb26-4ab7-b218-3dbe63206847" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_831fbb7e-6f2b-41ba-a272-9b3b289ef1ee" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_31632e83-eb26-4ab7-b218-3dbe63206847" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/IncomeTaxesLossBeforeProvisionforIncomeTaxesDetails" xlink:type="simple" xlink:href="bcrx-20241231.xsd#IncomeTaxesLossBeforeProvisionforIncomeTaxesDetails"/>
  <link:calculationLink xlink:role="http://www.biocryst.com/role/IncomeTaxesLossBeforeProvisionforIncomeTaxesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_339c4cf7-0c40-453c-939b-89bc9200c08a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign_db6d9412-875d-4b64-a4a6-0963edb27348" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_339c4cf7-0c40-453c-939b-89bc9200c08a" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign_db6d9412-875d-4b64-a4a6-0963edb27348" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic_8ea0de04-ad52-4df5-b392-2d14ababdcf0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_339c4cf7-0c40-453c-939b-89bc9200c08a" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic_8ea0de04-ad52-4df5-b392-2d14ababdcf0" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/IncomeTaxesScheduleofComponentsofIncomeTaxBenefitExpenseDetails" xlink:type="simple" xlink:href="bcrx-20241231.xsd#IncomeTaxesScheduleofComponentsofIncomeTaxBenefitExpenseDetails"/>
  <link:calculationLink xlink:role="http://www.biocryst.com/role/IncomeTaxesScheduleofComponentsofIncomeTaxBenefitExpenseDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredIncomeTaxExpenseBenefit_bed06ba8-db30-4b66-9d8a-81234d896e7d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredIncomeTaxExpenseBenefit"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredForeignIncomeTaxExpenseBenefit_9f71759e-8ed3-4292-ad56-dcce5b7746fc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredForeignIncomeTaxExpenseBenefit"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredIncomeTaxExpenseBenefit_bed06ba8-db30-4b66-9d8a-81234d896e7d" xlink:to="loc_us-gaap_DeferredForeignIncomeTaxExpenseBenefit_9f71759e-8ed3-4292-ad56-dcce5b7746fc" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredFederalStateAndLocalTaxExpenseBenefit_bf7535c1-1bd5-46f4-b5ef-683fdadd84a8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredFederalStateAndLocalTaxExpenseBenefit"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredIncomeTaxExpenseBenefit_bed06ba8-db30-4b66-9d8a-81234d896e7d" xlink:to="loc_us-gaap_DeferredFederalStateAndLocalTaxExpenseBenefit_bf7535c1-1bd5-46f4-b5ef-683fdadd84a8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CurrentIncomeTaxExpenseBenefit_238312f2-3324-4717-b0d5-9ef3a38f7fdb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CurrentIncomeTaxExpenseBenefit"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CurrentFederalStateAndLocalTaxExpenseBenefit_54edd681-14b1-4083-af3b-2abe6ea8de36" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CurrentFederalStateAndLocalTaxExpenseBenefit"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CurrentIncomeTaxExpenseBenefit_238312f2-3324-4717-b0d5-9ef3a38f7fdb" xlink:to="loc_us-gaap_CurrentFederalStateAndLocalTaxExpenseBenefit_54edd681-14b1-4083-af3b-2abe6ea8de36" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CurrentForeignTaxExpenseBenefit_fc5e2218-c70d-4762-a114-39c41adda9a4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CurrentForeignTaxExpenseBenefit"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CurrentIncomeTaxExpenseBenefit_238312f2-3324-4717-b0d5-9ef3a38f7fdb" xlink:to="loc_us-gaap_CurrentForeignTaxExpenseBenefit_fc5e2218-c70d-4762-a114-39c41adda9a4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_87bed688-1fc3-4bee-8814-0e0504cd2a4a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CurrentIncomeTaxExpenseBenefit_8985f680-d8f6-4667-823f-77c24abc4ebc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CurrentIncomeTaxExpenseBenefit"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_87bed688-1fc3-4bee-8814-0e0504cd2a4a" xlink:to="loc_us-gaap_CurrentIncomeTaxExpenseBenefit_8985f680-d8f6-4667-823f-77c24abc4ebc" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredIncomeTaxExpenseBenefit_fa0eb8a0-dede-4935-b76b-ba902e328004" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredIncomeTaxExpenseBenefit"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_87bed688-1fc3-4bee-8814-0e0504cd2a4a" xlink:to="loc_us-gaap_DeferredIncomeTaxExpenseBenefit_fa0eb8a0-dede-4935-b76b-ba902e328004" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/IncomeTaxesDifferencesBetweentheCompanysEffectiveTaxRateandtheStatutoryTaxRateDetails" xlink:type="simple" xlink:href="bcrx-20241231.xsd#IncomeTaxesDifferencesBetweentheCompanysEffectiveTaxRateandtheStatutoryTaxRateDetails"/>
  <link:calculationLink xlink:role="http://www.biocryst.com/role/IncomeTaxesDifferencesBetweentheCompanysEffectiveTaxRateandtheStatutoryTaxRateDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_fb9b8721-85e3-48f5-9ce2-299fbb8c97f5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxReconciliationOtherAdjustments_db635db5-edf8-40ad-b3c6-08ea48048caf" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxReconciliationOtherAdjustments"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_fb9b8721-85e3-48f5-9ce2-299fbb8c97f5" xlink:to="loc_us-gaap_IncomeTaxReconciliationOtherAdjustments_db635db5-edf8-40ad-b3c6-08ea48048caf" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxReconciliationNondeductibleExpense_98578eb3-f389-4c0e-8481-d47f49c0d9ff" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxReconciliationNondeductibleExpense"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_fb9b8721-85e3-48f5-9ce2-299fbb8c97f5" xlink:to="loc_us-gaap_IncomeTaxReconciliationNondeductibleExpense_98578eb3-f389-4c0e-8481-d47f49c0d9ff" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes_c9286e90-5c90-4fcb-9f66-dfe926aa0439" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_fb9b8721-85e3-48f5-9ce2-299fbb8c97f5" xlink:to="loc_us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes_c9286e90-5c90-4fcb-9f66-dfe926aa0439" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxReconciliationForeignIncomeTaxRateDifferential_dea59b35-e816-44b1-92d9-eefe7f8eabd5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxReconciliationForeignIncomeTaxRateDifferential"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_fb9b8721-85e3-48f5-9ce2-299fbb8c97f5" xlink:to="loc_us-gaap_IncomeTaxReconciliationForeignIncomeTaxRateDifferential_dea59b35-e816-44b1-92d9-eefe7f8eabd5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxReconciliationTaxCreditsResearch_ae5f5765-8c6b-482b-8dd8-8cb6a3effa19" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxReconciliationTaxCreditsResearch"/>
    <link:calculationArc order="5" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_fb9b8721-85e3-48f5-9ce2-299fbb8c97f5" xlink:to="loc_us-gaap_IncomeTaxReconciliationTaxCreditsResearch_ae5f5765-8c6b-482b-8dd8-8cb6a3effa19" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxReconciliationIncomeTaxExpenseBenefitAtFederalStatutoryIncomeTaxRate_25d7ec9b-8c7a-492f-a535-73e1dd698122" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxReconciliationIncomeTaxExpenseBenefitAtFederalStatutoryIncomeTaxRate"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_fb9b8721-85e3-48f5-9ce2-299fbb8c97f5" xlink:to="loc_us-gaap_IncomeTaxReconciliationIncomeTaxExpenseBenefitAtFederalStatutoryIncomeTaxRate_25d7ec9b-8c7a-492f-a535-73e1dd698122" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxReconciliationChangeInDeferredTaxAssetsValuationAllowance_20da0bb3-a056-4066-ada0-8d0a8027ac23" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxReconciliationChangeInDeferredTaxAssetsValuationAllowance"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeTaxExpenseBenefit_fb9b8721-85e3-48f5-9ce2-299fbb8c97f5" xlink:to="loc_us-gaap_IncomeTaxReconciliationChangeInDeferredTaxAssetsValuationAllowance_20da0bb3-a056-4066-ada0-8d0a8027ac23" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/IncomeTaxesDeferredTaxAssetsandLiabilitiesDetails" xlink:type="simple" xlink:href="bcrx-20241231.xsd#IncomeTaxesDeferredTaxAssetsandLiabilitiesDetails"/>
  <link:calculationLink xlink:role="http://www.biocryst.com/role/IncomeTaxesDeferredTaxAssetsandLiabilitiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredIncomeTaxLiabilities_0923bf06-4cb7-461f-92dd-eeae4b239d46" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredIncomeTaxLiabilities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxLiabilitiesPropertyPlantAndEquipment_7b54b294-88ed-4dc1-9f43-e465345ae3c2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxLiabilitiesPropertyPlantAndEquipment"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredIncomeTaxLiabilities_0923bf06-4cb7-461f-92dd-eeae4b239d46" xlink:to="loc_us-gaap_DeferredTaxLiabilitiesPropertyPlantAndEquipment_7b54b294-88ed-4dc1-9f43-e465345ae3c2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_DeferredTaxLiabilitiesRightOfUseAssets_58d8fc1f-b034-4b5e-a5ca-4171cfe7417e" xlink:href="bcrx-20241231.xsd#bcrx_DeferredTaxLiabilitiesRightOfUseAssets"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredIncomeTaxLiabilities_0923bf06-4cb7-461f-92dd-eeae4b239d46" xlink:to="loc_bcrx_DeferredTaxLiabilitiesRightOfUseAssets_58d8fc1f-b034-4b5e-a5ca-4171cfe7417e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsGross_978be923-dbab-4da1-92ca-a4ed93e34d85" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsGross"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsInProcessResearchAndDevelopment_ce6bd578-cf78-49f4-8c88-8cba64a21131" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsInProcessResearchAndDevelopment"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredTaxAssetsGross_978be923-dbab-4da1-92ca-a4ed93e34d85" xlink:to="loc_us-gaap_DeferredTaxAssetsInProcessResearchAndDevelopment_ce6bd578-cf78-49f4-8c88-8cba64a21131" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsOperatingLossCarryforwardsDomestic_2eb1684f-bf9f-4adf-8367-068feae7b624" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsOperatingLossCarryforwardsDomestic"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredTaxAssetsGross_978be923-dbab-4da1-92ca-a4ed93e34d85" xlink:to="loc_us-gaap_DeferredTaxAssetsOperatingLossCarryforwardsDomestic_2eb1684f-bf9f-4adf-8367-068feae7b624" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsOther_53b7ffa2-4f57-4977-97cd-480edcc32ae6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsOther"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredTaxAssetsGross_978be923-dbab-4da1-92ca-a4ed93e34d85" xlink:to="loc_us-gaap_DeferredTaxAssetsOther_53b7ffa2-4f57-4977-97cd-480edcc32ae6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost_3329e12d-aa11-44d5-a2e4-c504e23ef6e8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredTaxAssetsGross_978be923-dbab-4da1-92ca-a4ed93e34d85" xlink:to="loc_us-gaap_DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost_3329e12d-aa11-44d5-a2e4-c504e23ef6e8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsTaxCreditCarryforwardsResearch_0870dd11-bb6b-4355-a9e9-96d0319bd3ea" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsTaxCreditCarryforwardsResearch"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredTaxAssetsGross_978be923-dbab-4da1-92ca-a4ed93e34d85" xlink:to="loc_us-gaap_DeferredTaxAssetsTaxCreditCarryforwardsResearch_0870dd11-bb6b-4355-a9e9-96d0319bd3ea" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_DeferredTaxAssetsRoyaltyIncome_0c50628d-5b64-480f-8ab3-a5d4e184aacb" xlink:href="bcrx-20241231.xsd#bcrx_DeferredTaxAssetsRoyaltyIncome"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredTaxAssetsGross_978be923-dbab-4da1-92ca-a4ed93e34d85" xlink:to="loc_bcrx_DeferredTaxAssetsRoyaltyIncome_0c50628d-5b64-480f-8ab3-a5d4e184aacb" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_DeferredTaxAssetsLeasingObligations_1d45bb5b-c51b-40bc-b6f5-8dc45b48bef3" xlink:href="bcrx-20241231.xsd#bcrx_DeferredTaxAssetsLeasingObligations"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredTaxAssetsGross_978be923-dbab-4da1-92ca-a4ed93e34d85" xlink:to="loc_bcrx_DeferredTaxAssetsLeasingObligations_1d45bb5b-c51b-40bc-b6f5-8dc45b48bef3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsLiabilitiesNet_bc40d36b-2c7c-4494-b140-d86d80060385" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsLiabilitiesNet"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsGross_18deefdb-6545-4a58-ae43-584e0c15dd3c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsGross"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredTaxAssetsLiabilitiesNet_bc40d36b-2c7c-4494-b140-d86d80060385" xlink:to="loc_us-gaap_DeferredTaxAssetsGross_18deefdb-6545-4a58-ae43-584e0c15dd3c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredIncomeTaxLiabilities_0a5fa94c-e2c2-4799-b1b6-a93b7e8dbfdc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredIncomeTaxLiabilities"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredTaxAssetsLiabilitiesNet_bc40d36b-2c7c-4494-b140-d86d80060385" xlink:to="loc_us-gaap_DeferredIncomeTaxLiabilities_0a5fa94c-e2c2-4799-b1b6-a93b7e8dbfdc" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsValuationAllowance_d3ae5e08-0c27-4df6-a43e-e79f26d1c5cd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsValuationAllowance"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_DeferredTaxAssetsLiabilitiesNet_bc40d36b-2c7c-4494-b140-d86d80060385" xlink:to="loc_us-gaap_DeferredTaxAssetsValuationAllowance_d3ae5e08-0c27-4df6-a43e-e79f26d1c5cd" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/SegmentInformationSegmentReportingInformationbySegmentDetails" xlink:type="simple" xlink:href="bcrx-20241231.xsd#SegmentInformationSegmentReportingInformationbySegmentDetails"/>
  <link:calculationLink xlink:role="http://www.biocryst.com/role/SegmentInformationSegmentReportingInformationbySegmentDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_70184944-138c-4408-a952-40cf75e99357" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_InterestAndOtherIncomeLoss_ae15e65d-1f2e-4bcd-a894-a51995fb579d" xlink:href="bcrx-20241231.xsd#bcrx_InterestAndOtherIncomeLoss"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_70184944-138c-4408-a952-40cf75e99357" xlink:to="loc_bcrx_InterestAndOtherIncomeLoss_ae15e65d-1f2e-4bcd-a894-a51995fb579d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_17ea5083-9ad2-42d0-a049-b7bdef25dd48" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_70184944-138c-4408-a952-40cf75e99357" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_17ea5083-9ad2-42d0-a049-b7bdef25dd48" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseNonoperating_7f6223c2-1e9b-41df-99b9-3f5d382d4f22" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InterestExpenseNonoperating"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_70184944-138c-4408-a952-40cf75e99357" xlink:to="loc_us-gaap_InterestExpenseNonoperating_7f6223c2-1e9b-41df-99b9-3f5d382d4f22" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_d2b1cf7b-a076-4a3e-ba43-9c9cd687e2f4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:calculationArc order="4" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_70184944-138c-4408-a952-40cf75e99357" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_d2b1cf7b-a076-4a3e-ba43-9c9cd687e2f4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_9a49777a-fbf0-4bb2-82d2-f6183b636409" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_70184944-138c-4408-a952-40cf75e99357" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_9a49777a-fbf0-4bb2-82d2-f6183b636409" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSold_058f3491-55a0-452f-ae1c-c8d9d9ae7747" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostOfGoodsAndServicesSold"/>
    <link:calculationArc order="6" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_70184944-138c-4408-a952-40cf75e99357" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSold_058f3491-55a0-452f-ae1c-c8d9d9ae7747" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_Royalty_919445d0-f6c2-4555-bf48-b8610eb9fb41" xlink:href="bcrx-20241231.xsd#bcrx_Royalty"/>
    <link:calculationArc order="7" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_70184944-138c-4408-a952-40cf75e99357" xlink:to="loc_bcrx_Royalty_919445d0-f6c2-4555-bf48-b8610eb9fb41" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingGeneralAndAdministrativeExpense_4315ec07-8ada-4aa0-94dd-18d263944405" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SellingGeneralAndAdministrativeExpense"/>
    <link:calculationArc order="8" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_70184944-138c-4408-a952-40cf75e99357" xlink:to="loc_us-gaap_SellingGeneralAndAdministrativeExpense_4315ec07-8ada-4aa0-94dd-18d263944405" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingOtherItemAmount_3bfaa0ad-c417-4bba-a8bc-3aea4890b811" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SegmentReportingOtherItemAmount"/>
    <link:calculationArc order="9" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_70184944-138c-4408-a952-40cf75e99357" xlink:to="loc_us-gaap_SegmentReportingOtherItemAmount_3bfaa0ad-c417-4bba-a8bc-3aea4890b811" xlink:type="arc"/>
  </link:calculationLink>
</link:linkbase>
