Abstract

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.

Details

Title
Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model
Author
Rosenke Kyle 1 ; Hansen, Frederick 1 ; Schwarz, Benjamin 2 ; Feldmann Friederike 3 ; Haddock, Elaine 1 ; Rosenke Rebecca 3 ; Barbian Kent 4 ; Meade-White, Kimberly 1 ; Okumura Atsushi 1 ; Leventhal Shanna 1 ; Hawman, David W 1 ; Ricotta, Emily 5   VIAFID ORCID Logo  ; Bosio, Catharine M 2 ; Martens, Craig 4 ; Saturday Greg 3 ; Feldmann Heinz 1   VIAFID ORCID Logo  ; Jarvis, Michael A 6   VIAFID ORCID Logo 

1  National Institutes of Health, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, Hamilton, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) 
2  National Institutes of Health, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, Hamilton, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) 
3  National Institutes of Health, Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, Hamilton, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) 
4  National Institutes of Health, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, Hamilton, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) 
5  National Institutes of Health, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) 
6  National Institutes of Health, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, Hamilton, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165); University of Plymouth, Plymouth, UK (GRID:grid.11201.33) (ISNI:0000 0001 2219 0747); The Vaccine Group Ltd, Plymouth, UK (GRID:grid.11201.33) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-021-22580-8
ProQuest document ID
2513413903
Copyright
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.