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

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

doi:10.1038/s41467-021-22580-8

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

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

^*Corresponding author for this work

Preventive Medicine and Biostatistics

Research output: Contribution to journal › Article › peer-review

118 Scopus citations

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.

Original language	English
Article number	2295
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-22580-8
State	Published - 1 Dec 2021

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Rosenke, K., Hansen, F., Schwarz, B., Feldmann, F., Haddock, E., Rosenke, R., Barbian, K., Meade-White, K., Okumura, A., Leventhal, S., Hawman, D. W., Ricotta, E., Bosio, C. M., Martens, C., Saturday, G., Feldmann, H., & Jarvis, M. A. (2021). Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model. Nature Communications, 12(1), Article 2295. https://doi.org/10.1038/s41467-021-22580-8

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title = "Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2021, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.",

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Rosenke, K, Hansen, F, Schwarz, B, Feldmann, F, Haddock, E, Rosenke, R, Barbian, K, Meade-White, K, Okumura, A, Leventhal, S, Hawman, DW, Ricotta, E, Bosio, CM, Martens, C, Saturday, G, Feldmann, H & Jarvis, MA 2021, 'Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model', Nature Communications, vol. 12, no. 1, 2295. https://doi.org/10.1038/s41467-021-22580-8

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AU - Rosenke, Kyle

AU - Hansen, Frederick

AU - Schwarz, Benjamin

AU - Feldmann, Friederike

AU - Haddock, Elaine

AU - Rosenke, Rebecca

AU - Barbian, Kent

AU - Meade-White, Kimberly

AU - Okumura, Atsushi

AU - Leventhal, Shanna

AU - Hawman, David W.

AU - Ricotta, Emily

AU - Bosio, Catharine M.

AU - Martens, Craig

AU - Saturday, Greg

AU - Feldmann, Heinz

AU - Jarvis, Michael A.

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

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VL - 12

JO - Nature Communications

JF - Nature Communications

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

Abstract

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