Bemnifosbuvir (AT-527, RO7496998) is an antiviral drug invented by Atea Pharmaceuticals and licensed to Roche for clinical development, a novel nucleotide analog prodrug originally developed for the treatment of hepatitis C.[1][2] Bemnifosbuvir is the orally bioavailable hemisulfate salt of AT-511, which is metabolized in several steps to the active nucleotide triphosphate AT-9010, acting as an RNA polymerase inhibitor and thereby interfering with viral replication. Bemnifosbuvir has been researched for the treatment of coronavirus diseases such as that produced by SARS-CoV-2.[3] It showed good results in early clinical trials but had inconsistent results at later stages.[4][5] Bemnifosbuvir's Phase III study ended early as it failed to meet its primary endpoint of symptom alleviation and did not decrease viral load. However, the drug was well-tolerated and reduced relative hospitalization risk by 71%.[6]

Bemnifosbuvir
Clinical data
Other namesAT-527, AT-511
Legal status
Legal status
Identifiers
  • Propan-2-yl (2S)-2-[[[(2R,3R,4R,5R)-5-[2-amino-6-(methylamino)purin-9-yl]-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
Chemical and physical data
FormulaC24H33FN7O7P
Molar mass581.542 g·mol−1
3D model (JSmol)
  • C[C@@H](C(=O)OC(C)C)NP(=O)(OC[C@@H]1[C@H]([C@@]([C@@H](O1)N2C=NC3=C(N=C(N=C32)N)NC)(C)F)O)OC4=CC=CC=C4
  • InChI=1S/C24H33FN7O7P/c1-13(2)37-21(34)14(3)31-40(35,39-15-9-7-6-8-10-15)36-11-16-18(33)24(4,25)22(38-16)32-12-28-17-19(27-5)29-23(26)30-20(17)32/h6-10,12-14,16,18,22,33H,11H2,1-5H3,(H,31,35)(H3,26,27,29,30)/t14-,16+,18+,22+,24+,40?/m0/s1
  • Key:OISLSHLAXHALQZ-HEOQURLSSA-N

See also

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References

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  1. ^ Berliba E, Bogus M, Vanhoutte F, Berghmans PJ, Good SS, Moussa A, et al. (September 2019). "Safety, pharmacokinetics and antiviral activity of AT-527, a novel purine nucleotide prodrug, in HCV-infected subjects with and without cirrhosis". Antimicrobial Agents and Chemotherapy. 63 (12). doi:10.1128/AAC.01201-19. PMC 6879261. PMID 31570394.
  2. ^ Good SS, Moussa A, Zhou XJ, Pietropaolo K, Sommadossi JP (2020). "Preclinical evaluation of AT-527, a novel guanosine nucleotide prodrug with potent, pan-genotypic activity against hepatitis C virus". PLOS ONE. 15 (1): e0227104. Bibcode:2020PLoSO..1527104G. doi:10.1371/journal.pone.0227104. PMC 6949113. PMID 31914458.
  3. ^ Good SS, Westover J, Jung KH, Zhou XJ, Moussa A, La Colla P, et al. (March 2021). "AT-527, a Double Prodrug of a Guanosine Nucleotide Analog, Is a Potent Inhibitor of SARS-CoV-2 In Vitro and a Promising Oral Antiviral for Treatment of COVID-19". Antimicrobial Agents and Chemotherapy. 65 (4). doi:10.1128/AAC.02479-20. PMC 8097421. PMID 33558299.
  4. ^ Lowe D (19 October 2021). "AT-527 Fails a Phase II". In the Pipeline. Science.org.
  5. ^ Fidler B, Gardner J (19 October 2021). "Atea, Roche change plans for oral COVID-19 drug after trial setback". Biopharmadive.com.
  6. ^ Horga A, Saenz R, Yilmaz G, Simón-Campos A, Pietropaolo K, Stubbings WJ, Collinson N, Ishak L, Zrinscak B, Belanger B, Granier C, Lin K, C Hurt A, Zhou XJ, Wildum S, Hammond J (November 2023). "Oral bemnifosbuvir (AT-527) vs placebo in patients with mild-to-moderate COVID-19 in an outpatient setting (MORNINGSKY)". Future Virology. 18 (13). doi:10.2217/fvl-2023-0115. PMC 10621114. PMID 37928891.