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

Author

Listed:
  • Kyle Rosenke

    (National Institutes of Health)

  • Frederick Hansen

    (National Institutes of Health)

  • Benjamin Schwarz

    (National Institutes of Health)

  • Friederike Feldmann

    (National Institutes of Health)

  • Elaine Haddock

    (National Institutes of Health)

  • Rebecca Rosenke

    (National Institutes of Health)

  • Kent Barbian

    (National Institutes of Health)

  • Kimberly Meade-White

    (National Institutes of Health)

  • Atsushi Okumura

    (National Institutes of Health)

  • Shanna Leventhal

    (National Institutes of Health)

  • David W. Hawman

    (National Institutes of Health)

  • Emily Ricotta

    (National Institutes of Health)

  • Catharine M. Bosio

    (National Institutes of Health)

  • Craig Martens

    (National Institutes of Health)

  • Greg Saturday

    (National Institutes of Health)

  • Heinz Feldmann

    (National Institutes of Health)

  • Michael A. Jarvis

    (National Institutes of Health
    University of Plymouth
    The Vaccine Group Ltd)

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.

Suggested Citation

  • Kyle Rosenke & Frederick Hansen & Benjamin Schwarz & Friederike Feldmann & Elaine Haddock & Rebecca Rosenke & Kent Barbian & Kimberly Meade-White & Atsushi Okumura & Shanna Leventhal & David W. Hawman, 2021. "Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model," Nature Communications, Nature, vol. 12(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22580-8
    DOI: 10.1038/s41467-021-22580-8
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    Cited by:

    1. Carolin M. Lieber & Robert M. Cox & Julien Sourimant & Josef D. Wolf & Kate Juergens & Quynh Phung & Manohar T. Saindane & Meghan K. Smith & Zachary M. Sticher & Alexander A. Kalykhalov & Michael G. N, 2022. "SARS-CoV-2 VOC type and biological sex affect molnupiravir efficacy in severe COVID-19 dwarf hamster model," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Ankita Leekha & Arash Saeedi & Monish Kumar & K. M. Samiur Rahman Sefat & Melisa Martinez-Paniagua & Hui Meng & Mohsen Fathi & Rohan Kulkarni & Kate Reichel & Sujit Biswas & Daphne Tsitoura & Xinli Li, 2024. "An intranasal nanoparticle STING agonist protects against respiratory viruses in animal models," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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