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Discovery of GS-5245 (Obeldesivir), an Oral Prodrug of Nucleoside GS-441524 That Exhibits Antiviral Efficacy in SARS-CoV-2-Infected African Green Monkeys.
Mackman RL, Kalla RV, Babusis D, Pitts J, Barrett KT, Chun K, Du Pont V, Rodriguez L, Moshiri J, Xu Y, Lee M, Lee G, Bleier B, Nguyen AQ, O'Keefe BM, Ambrosi A, Cook M, Yu J, Dempah KE, Bunyan E, Riola NC, Lu X, Liu R, Davie A, Hsiang TY, Dearing J, Vermillion M, Gale M Jr, Niedziela-Majka A, Feng JY, Hedskog C, Bilello JP, Subramanian R, Cihlar T. Mackman RL, et al. Among authors: du pont v. J Med Chem. 2023 Sep 14;66(17):11701-11717. doi: 10.1021/acs.jmedchem.3c00750. Epub 2023 Aug 19. J Med Chem. 2023. PMID: 37596939 Free PMC article.
Remdesivir and GS-441524 Retain Antiviral Activity against Delta, Omicron, and Other Emergent SARS-CoV-2 Variants.
Pitts J, Li J, Perry JK, Du Pont V, Riola N, Rodriguez L, Lu X, Kurhade C, Xie X, Camus G, Manhas S, Martin R, Shi PY, Cihlar T, Porter DP, Mo H, Maiorova E, Bilello JP. Pitts J, et al. Among authors: du pont v. Antimicrob Agents Chemother. 2022 Jun 21;66(6):e0022222. doi: 10.1128/aac.00222-22. Epub 2022 May 9. Antimicrob Agents Chemother. 2022. PMID: 35532238 Free PMC article.
Therapeutic treatment with an oral prodrug of the remdesivir parental nucleoside is protective against SARS-CoV-2 pathogenesis in mice.
Schäfer A, Martinez DR, Won JJ, Meganck RM, Moreira FR, Brown AJ, Gully KL, Zweigart MR, Conrad WS, May SR, Dong S, Kalla R, Chun K, Du Pont V, Babusis D, Tang J, Murakami E, Subramanian R, Barrett KT, Bleier BJ, Bannister R, Feng JY, Bilello JP, Cihlar T, Mackman RL, Montgomery SA, Baric RS, Sheahan TP. Schäfer A, et al. Among authors: du pont v. Sci Transl Med. 2022 May 4;14(643):eabm3410. doi: 10.1126/scitranslmed.abm3410. Epub 2022 May 4. Sci Transl Med. 2022. PMID: 35315683 Free PMC article.
Oral prodrug of remdesivir parent GS-441524 is efficacious against SARS-CoV-2 in ferrets.
Cox RM, Wolf JD, Lieber CM, Sourimant J, Lin MJ, Babusis D, DuPont V, Chan J, Barrett KT, Lye D, Kalla R, Chun K, Mackman RL, Ye C, Cihlar T, Martinez-Sobrido L, Greninger AL, Bilello JP, Plemper RK. Cox RM, et al. Nat Commun. 2021 Nov 5;12(1):6415. doi: 10.1038/s41467-021-26760-4. Nat Commun. 2021. PMID: 34741049 Free PMC article.
Therapeutic efficacy of an oral nucleoside analog of remdesivir against SARS-CoV-2 pathogenesis in mice.
Schäfer A, Martinez DR, Won JJ, Moreira FR, Brown AJ, Gully KL, Kalla R, Chun K, Du Pont V, Babusis D, Tang J, Murakami E, Subramanian R, Barrett KT, Bleier BJ, Bannister R, Feng JY, Bilello JP, Cihlar T, Mackman RL, Montgomery SA, Baric RS, Sheahan TP. Schäfer A, et al. Among authors: du pont v. bioRxiv [Preprint]. 2021 Sep 17:2021.09.13.460111. doi: 10.1101/2021.09.13.460111. bioRxiv. 2021. Update in: Sci Transl Med. 2022 May 4;14(643):eabm3410. doi: 10.1126/scitranslmed.abm3410 PMID: 34545367 Free PMC article. Updated. Preprint.
Prodrugs of a 1'-CN-4-Aza-7,9-dideazaadenosine C-Nucleoside Leading to the Discovery of Remdesivir (GS-5734) as a Potent Inhibitor of Respiratory Syncytial Virus with Efficacy in the African Green Monkey Model of RSV.
Mackman RL, Hui HC, Perron M, Murakami E, Palmiotti C, Lee G, Stray K, Zhang L, Goyal B, Chun K, Byun D, Siegel D, Simonovich S, Du Pont V, Pitts J, Babusis D, Vijjapurapu A, Lu X, Kim C, Zhao X, Chan J, Ma B, Lye D, Vandersteen A, Wortman S, Barrett KT, Toteva M, Jordan R, Subramanian R, Bilello JP, Cihlar T. Mackman RL, et al. Among authors: du pont v. J Med Chem. 2021 Apr 22;64(8):5001-5017. doi: 10.1021/acs.jmedchem.1c00071. Epub 2021 Apr 9. J Med Chem. 2021. PMID: 33835812
Remdesivir Inhibits SARS-CoV-2 in Human Lung Cells and Chimeric SARS-CoV Expressing the SARS-CoV-2 RNA Polymerase in Mice.
Pruijssers AJ, George AS, Schäfer A, Leist SR, Gralinksi LE, Dinnon KH 3rd, Yount BL, Agostini ML, Stevens LJ, Chappell JD, Lu X, Hughes TM, Gully K, Martinez DR, Brown AJ, Graham RL, Perry JK, Du Pont V, Pitts J, Ma B, Babusis D, Murakami E, Feng JY, Bilello JP, Porter DP, Cihlar T, Baric RS, Denison MR, Sheahan TP. Pruijssers AJ, et al. Among authors: du pont v. Cell Rep. 2020 Jul 21;32(3):107940. doi: 10.1016/j.celrep.2020.107940. Epub 2020 Jul 7. Cell Rep. 2020. PMID: 32668216 Free PMC article.
Remdesivir potently inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice.
Pruijssers AJ, George AS, Schäfer A, Leist SR, Gralinksi LE, Dinnon KH, Yount BL, Agostini ML, Stevens LJ, Chappell JD, Lu X, Hughes TM, Gully K, Martinez DR, Brown AJ, Graham RL, Perry JK, Du Pont V, Pitts J, Ma B, Babusis D, Murakami E, Feng JY, Bilello JP, Porter DP, Cihlar T, Baric RS, Denison MR, Sheahan TP. Pruijssers AJ, et al. Among authors: du pont v. bioRxiv [Preprint]. 2020 Apr 27:2020.04.27.064279. doi: 10.1101/2020.04.27.064279. bioRxiv. 2020. Update in: Cell Rep. 2020 Jul 21;32(3):107940. doi: 10.1016/j.celrep.2020.107940 PMID: 32511392 Free PMC article. Updated. Preprint.
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