R., Gralinski L. administration of GS-621763 translated to dose-dependent antiviral activity in mice infected with SARS-CoV-2. Restorative GS-621763 administration reduced viral weight and lung pathology; treatment also improved pulmonary function in COVID-19 mouse MGCD0103 (Mocetinostat) model. A direct assessment of GS-621763 with molnupiravir, an oral nucleoside analog antiviral which has recently received EUA authorization, proved both medicines to be similarly efficacious in mice. These data support the exploration of GS-441524 oral prodrugs for the treatment of COVID-19. INTRODUCTION Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 and offers caused over 450 million infections and over 6 million deaths worldwide as of March 2022 ( and a Promising Dental Antiviral for Treatment of COVID-19. Antimicrob. Providers Chemother. 65, e02479-20 (2021). 10.1128/AAC.02479-20 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 27. Pruijssers A. J., George A. S., Sch?fer A., Leist S. R., Gralinksi L. E., Dinnon K. H. 3rd, Yount B. L., Agostini M. L., Stevens L. J., Chappell J. Rabbit Polyclonal to KR2_VZVD D., Lu X., Hughes T. M., Gully K., Martinez D. R., Brown A. J., Graham R. L., Perry J. K., Du Pont V., Pitts J., Ma B., Babusis D., Murakami E., Feng J. Y., Bilello J. P., Porter D. P., Cihlar T., Baric R. S., Denison M. R., Sheahan T. P., Remdesivir Inhibits SARS-CoV-2 in Human being Lung Cells and Chimeric SARS-CoV Expressing the SARS-CoV-2 RNA Polymerase in Mice. Cell Rep. 32, 107940 (2020). 10.1016/j.celrep.2020.107940 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 28. Mackman R. L., Hui H. C., 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 K. T., Toteva M., Jordan R., Subramanian R., Bilello J. P., Cihlar T., Prodrugs of a 1-CN-4-Aza-7,9-dideazaadenosine em C /em -Nucleoside Leading to the Finding of Remdesivir (GS-5734) like a Potent Inhibitor of Respiratory Syncytial Computer virus with Effectiveness in the African Green Monkey Model of RSV. J. Med. Chem. 64, 5001C5017 (2021). 10.1021/acs.jmedchem.1c00071 [PubMed] [CrossRef] [Google Scholar] 29. Hou Y. J., Okuda K., Edwards C. E., Martinez D. R., Asakura T., Dinnon K. H. 3rd, Kato T., Lee R. E., Yount B. L., Mascenik T. M., Chen G., Olivier K. N., Ghio A., Tse L. V., Leist S. R., Gralinski L. E., Sch?fer A., Dang H., Gilmore R., Nakano S., Sun MGCD0103 (Mocetinostat) L., Fulcher M. L., Livraghi-Butrico A., Nicely N. I., Cameron M., Cameron C., Kelvin D. J., de Silva A., Margolis D. M., Markmann A., Bartelt L., Zumwalt R., Martinez F. J., Salvatore S. P., Borczuk A., Tata P. R., Sontake V., Kimple A., Jaspers I., ONeal W. K., Randell S. H., Boucher R. C., Baric R. S., SARS-CoV-2 Reverse Genetics Reveals a Variable Illness Gradient in the Respiratory Tract. Cell 182, 429C446.e14 (2020). 10.1016/j.cell.2020.05.042 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 30. Xie X., Muruato A. E., Zhang X., Lokugamage K. G., Fontes-Garfias C. R., Zou J., Liu J., Ren P., Balakrishnan M., Cihlar T., Tseng C. K., Makino S., Menachery V. D., Bilello J. P., Shi P. Y., A nanoluciferase SARS-CoV-2 for quick neutralization screening and testing of anti-infective medicines for COVID-19. Nat. Commun. 11, 5214 (2020). 10.1038/s41467-020-19055-7 [PMC free article] [PubMed] [CrossRef] MGCD0103 (Mocetinostat) [Google Scholar] 31. Leist S. R., Dinnon K. H. 3rd, Sch?fer A., Tse L. V., Okuda K., Hou Y. J., Western A., Edwards C. E., Sanders W., Fritch E. J., Gully K. L., Scobey T., Brown A. J., Sheahan T. P., Moorman N. J., Boucher R. C., Gralinski L. E., Montgomery S. A., Baric R. S., A Mouse-Adapted SARS-CoV-2 Induces Acute Lung Injury and Mortality in Standard Laboratory Mice. Cell 183, 1070C1085.e12 (2020). 10.1016/j.cell.2020.09.050 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 32. Cox R. M., Wolf J. D., Lieber C. M., Sourimant J., Lin M. J., Babusis D., DuPont V., Chan J., Barrett K. T., Lye D., Kalla R., Chun K., Mackman R. L., Ye C., Cihlar T., Martinez-Sobrido L., Greninger.