Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses
Timothy P. Sheahan(University of North Carolina at Chapel Hill), Amy Sims(University of North Carolina at Chapel Hill), Rachel L. Graham(University of North Carolina at Chapel Hill), Vineet D. Menachery(University of North Carolina at Chapel Hill), Lisa E. Gralinski(University of North Carolina at Chapel Hill), James Brett Case(Vanderbilt University Medical Center), Sarah R. Leist(University of North Carolina at Chapel Hill), Krzysztof Pyrć(Jagiellonian University), Joy Y. Feng(Gilead Sciences (United States)), Iva Trantcheva(Gilead Sciences (United States)), Roy Bannister(Gilead Sciences (United States)), Yeojin Park(Gilead Sciences (United States)), Darius Babusis(Gilead Sciences (United States)), Michael O. Clarke(Gilead Sciences (United States)), Richard L. Mackman(Gilead Sciences (United States)), Jamie E. Spahn(Gilead Sciences (United States)), Christopher A. Palmiotti(Gilead Sciences (United States)), Dustin S. Siegel(Gilead Sciences (United States)), Adrian S. Ray(Gilead Sciences (United States)), Tomáš Cihlář(Gilead Sciences (United States)), Robert Jordan(Gilead Sciences (United States)), Mark R. Denison(Vanderbilt University Medical Center), Ralph S. Baric(University of North Carolina at Chapel Hill)
Cited by 1,630Open Access
Abstract
values. GS-5734 was also effective against bat CoVs, prepandemic bat CoVs, and circulating contemporary human CoV in primary human lung cells, thus demonstrating broad-spectrum anti-CoV activity. In a mouse model of SARS-CoV pathogenesis, prophylactic and early therapeutic administration of GS-5734 significantly reduced lung viral load and improved clinical signs of disease as well as respiratory function. These data provide substantive evidence that GS-5734 may prove effective against endemic MERS-CoV in the Middle East, circulating human CoV, and, possibly most importantly, emerging CoV of the future.
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