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

by Jarvis, Michael A. , Barbian, Kent , Feldmann, Heinz , Feldmann, Friederike , Leventhal, Shanna , Bosio, Catharine M. , Okumura, Atsushi , Hansen, Frederick , Haddock, Elaine , Schwarz, Benjamin , Ricotta, Emily , Rosenke, Rebecca , Hawman, David W. , Martens, Craig , Saturday, Greg , Meade-White, Kimberly , Rosenke, Kyle

in 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 / Antiviral drugs / 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 coronavirus 2 / Vero Cells / Viral diseases / Virus Replication - drug effects

2021

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

2021

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

2021

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Journal Article

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

Jarvis, Michael A.,

Barbian, Kent,

Feldmann, Heinz,

Feldmann, Friederike,

Leventhal, Shanna,

Bosio, Catharine M.,

Okumura, Atsushi,

Hansen, Frederick,

Haddock, Elaine,

Schwarz, Benjamin,

Ricotta, Emily,

Rosenke, Rebecca,

Hawman, David W.,

Martens, Craig,

Saturday, Greg,

Meade-White, Kimberly,

Rosenke, Kyle

2021

Overview

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.

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Publisher

Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

Subject

13/106

/ 38/1

/ 38/77

/ 631/326/22/1295

/ 631/326/596/4130

/ 82/51

/ Administration, Oral