Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease

• Published in: mBio Vol. 9; no. 2
• Main Authors: Agostini, Maria L., Andres, Erica L., Sims, Amy C., Graham, Rachel L., Sheahan, Timothy P., Lu, Xiaotao, Smith, Everett Clinton, Case, James Brett, Feng, Joy Y., Jordan, Robert, Ray, Adrian S., Cihlar, Tomas, Siegel, Dustin, Mackman, Richard L., Clarke, Michael O., Baric, Ralph S., Denison, Mark R.
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 06.03.2018
• Subjects: Alanine - analogs & derivatives; Alanine - pharmacology; Animals; antiviral agents; Antiviral Agents - pharmacology; antiviral resistance; coronavirus; Coronavirus - drug effects; Coronavirus - enzymology; Exoribonucleases - chemistry; Exoribonucleases - genetics; Exoribonucleases - metabolism; Mice; Mutation - genetics; nucleoside analogs; Ribonucleotides - pharmacology; RNA polymerases; SARS Virus - drug effects; SARS Virus - genetics; SARS-CoV; Virus Replication - drug effects; Virus Replication - genetics; antiviral resistance; nucleoside analogs; antiviral agents; SARS-CoV; coronavirus; pandemic; RNA polymerases

Emerging coronaviruses (CoVs) cause severe disease in humans, but no approved therapeutics are available. The CoV nsp14 exoribonuclease (ExoN) has complicated development of antiviral nucleosides due to its proofreading activity. We recently reported that the nucleoside analogue GS-5734 (remdesivir)...