An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice

• Published in: Science translational medicine Vol. 12; no. 541
• Main Authors: Sheahan, Timothy P, Sims, Amy C, Zhou, Shuntai, Graham, Rachel L, Pruijssers, Andrea J, Agostini, Maria L, Leist, Sarah R, Schäfer, Alexandra, Dinnon, 3rd, Kenneth H, Stevens, Laura J, Chappell, James D, Lu, Xiaotao, Hughes, Tia M, George, Amelia S, Hill, Collin S, Montgomery, Stephanie A, Brown, Ariane J, Bluemling, Gregory R, Natchus, Michael G, Saindane, Manohar, Kolykhalov, Alexander A, Painter, George, Harcourt, Jennifer, Tamin, Azaibi, Thornburg, Natalie J, Swanstrom, Ronald, Denison, Mark R, Baric, Ralph S
• Format: Journal Article
• Language: English
• Published: United States 29.04.2020
• Subjects: Adenosine Monophosphate - administration & dosage; Adenosine Monophosphate - analogs & derivatives; Alanine - administration & dosage; Alanine - analogs & derivatives; Animals; Antibiotic Prophylaxis; Antiviral Agents - administration & dosage; Betacoronavirus - physiology; Cell Line; Coronavirus Infections - drug therapy; Coronavirus Infections - pathology; COVID-19; Cytidine - administration & dosage; Cytidine - analogs & derivatives; Disease Models, Animal; Drug Resistance, Viral; Humans; Hydroxylamines; Lung - pathology; Mice; Mice, Inbred C57BL; Middle East Respiratory Syndrome Coronavirus - physiology; Models, Molecular; Mutation - drug effects; Pandemics; Pneumonia, Viral - drug therapy; Pneumonia, Viral - pathology; Primary Cell Culture; Random Allocation; Respiratory System - cytology; Ribonucleosides - administration & dosage; RNA, Viral; RNA-Dependent RNA Polymerase - chemistry; RNA-Dependent RNA Polymerase - genetics; SARS-CoV-2; Virus Replication - drug effects

Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2, the causative agent of COVID-19. Here, we show that the ribonucleoside analog β-d-N -hydroxycytidine (NHC; EIDD-1931) has broad-spectrum antiviral...