2. Academic Validation
  3. Drug susceptibility and the potential for drug-resistant SARS-CoV-2 emergence in immunocompromised animals

Drug susceptibility and the potential for drug-resistant SARS-CoV-2 emergence in immunocompromised animals

  • iScience. 2024 Aug 17;27(9):110729. doi: 10.1016/j.isci.2024.110729.
Maki Kiso 1,  Ryuta Uraki 1 2 3,  Seiya Yamayoshi 1 2 3 4,  Masaki Imai 2 3 4,  Yoshihiro Kawaoka 1 2 3 5
Affiliations

Affiliations

  • 1 Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), The University of Tokyo, Tokyo 108-8639, Japan.
  • 2 Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
  • 3 The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo 162-8655, Japan.
  • 4 International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
  • 5 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.
PMID: 39280602 DOI: 10.1016/j.isci.2024.110729
Abstract

The reduced susceptibility of mRNA vaccines and diminished neutralizing activity of therapeutic monoclonal Antibodies against Omicron variants, including BQ.1.1, XBB, and their descendants, highlight the importance of Antiviral therapies. Here, we assessed the efficacy of two antivirals, molnupiravir, targeting a viral RNA-dependent RNA polymerase, and nirmatrelvir, targeting a main Protease, against BQ.1.1 in hamsters. We found that prophylactic or therapeutic treatment with either drug significantly reduced the viral load in the lungs of infected hamsters. We also evaluated the risk of emergence of drug-resistant viruses in immunocompromised hamsters. Although 13 days of drug treatment reduced viral titers, the immunocompromised hosts could not completely clear the virus. Viruses isolated from drug-treated immunocompromised hamsters did not show reduced susceptibility to the drugs. Molnupiravir and nirmatrelvir remain effective in vivo against variants with reduced susceptibility to monoclonal Antibodies and mRNA vaccine-induced Antibodies, with limited emergence of drug-resistant variants under the conditions tested.

Keywords

Immunology; Virology.

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