Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model

• Published in: Nature communications Vol. 12; no. 1; p. 2295
• Main Authors: Rosenke, Kyle, Hansen, Frederick, Schwarz, Benjamin, Feldmann, Friederike, Haddock, Elaine, Rosenke, Rebecca, Barbian, Kent, Meade-White, Kimberly, Okumura, Atsushi, Leventhal, Shanna, Hawman, David W., Ricotta, Emily, Bosio, Catharine M., Martens, Craig, Saturday, Greg, Feldmann, Heinz, Jarvis, Michael A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.04.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 38/1; 38/77; 631/326/22/1295; 631/326/596/4130; 82/51; Administration, Oral; Animals; Antiviral agents; Antiviral Agents - administration & dosage; Chlorocebus aethiops; Coronaviruses; COVID-19; COVID-19 - drug therapy; COVID-19 - virology; Cytidine - administration & dosage; Cytidine - analogs & derivatives; Disease Models, Animal; Exposure; Humanities and Social Sciences; Humans; Hydroxylamines - administration & dosage; Infections; Mesocricetus; Model testing; multidisciplinary; Nucleoside analogs; Nucleosides; Oral administration; Pandemics; Replication; Risk; Risk exposure; SARS-CoV-2 - drug effects; SARS-CoV-2 - isolation & purification; SARS-CoV-2 - physiology; Science; Science (multidisciplinary); Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Vaccines; Vero Cells; Viral diseases; Virus Replication - drug effects
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-22580-8

The COVID-19 pandemic progresses unabated in many regions of the world. An effective antiviral against SARS-CoV-2 that could be administered orally for use following high-risk exposure would be of substantial benefit in controlling the COVID-19 pandemic. Herein, we show that MK-4482, an orally administered nucleoside analog, inhibits SARS-CoV-2 replication in the Syrian hamster model. The inhibitory effect of MK-4482 on SARS-CoV-2 replication is observed in animals when the drug is administered either beginning 12 h before or 12 h following infection in a high-risk exposure model. These data support the potential utility of MK-4482 to control SARS-CoV-2 infection in humans following high-risk exposure as well as for treatment of COVID-19 patients. While vaccines protecting against SARS-CoV-2 infection are approved, currently, there are no drugs suitable for high-risk exposure use against SARS-CoV-2. Here, Rosenke et al. provide evidence that orally delivered MK-4482, a nucleoside analog, inhibits SARS-CoV-2 replication in the Syrian hamster model.