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

K Rosenke; Frederick Hansen; Benjamin Schwarz; F Feldmann; Elaine Haddock; R Rosenke; Kent Barbian; Kimberly Meade-White; Atsushi Okumura; Shanna Leventhal; David W. Hawman; Emily Ricotta; Catharine M. Bosio; Craig Martens; Greg Saturday; H 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

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

^*Corresponding author for this work

School of Biomedical Sciences

National Institutes of Health
The Vaccine Group

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

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Abstract

AbstractThe 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
Number of pages	0
Journal	Nature Communications
Volume	12
Issue number	1
Early online date	16 Apr 2021
DOIs	https://doi.org/10.1038/s41467-021-22580-8
Publication status	Published - 16 Apr 2021

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SDG 3 Good Health and Well-being

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10.1038/s41467-021-22580-8

Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster modelFinal published version, 1.75 MB

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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). https://doi.org/10.1038/s41467-021-22580-8

@article{2f096b350fa34a23961d29cb58362e03,

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

abstract = "AbstractThe 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 = "K Rosenke and Frederick Hansen and Benjamin Schwarz and F Feldmann and Elaine Haddock and R 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 H Feldmann and Jarvis, \{Michael A.\}",

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day = "16",

doi = "10.1038/s41467-021-22580-8",

language = "English",

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journal = "Nature Communications",

issn = "2041-1723",

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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. https://doi.org/10.1038/s41467-021-22580-8

TY - JOUR

T1 - Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model

AU - Rosenke, K

AU - Hansen, Frederick

AU - Schwarz, Benjamin

AU - Feldmann, F

AU - Haddock, Elaine

AU - Rosenke, R

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, H

AU - Jarvis, Michael A.

PY - 2021/4/16

Y1 - 2021/4/16

N2 - AbstractThe 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 - AbstractThe 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.

UR - https://pearl.plymouth.ac.uk/bhs-research/219/

U2 - 10.1038/s41467-021-22580-8

DO - 10.1038/s41467-021-22580-8

M3 - Article

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

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

Abstract

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