2. Academic Validation
  3. Therapeutic efficacy of monoclonal antibodies and antivirals against SARS-CoV-2 Omicron BA.1 in Syrian hamsters

Therapeutic efficacy of monoclonal antibodies and antivirals against SARS-CoV-2 Omicron BA.1 in Syrian hamsters

  • Nat Microbiol. 2022 Aug;7(8):1252-1258. doi: 10.1038/s41564-022-01170-4.
Ryuta Uraki  # 1 2,  Maki Kiso  # 1,  Masaki Imai  # 1 2,  Seiya Yamayoshi 1 2,  Mutsumi Ito 1,  Seiichiro Fujisaki 3,  Emi Takashita 3,  Michiko Ujie 1 2,  Yuri Furusawa 1 2,  Atsuhiro Yasuhara 1,  Kiyoko Iwatsuki-Horimoto 1,  Yuko Sakai-Tagawa 1,  Shinji Watanabe 3,  Hideki Hasegawa 3,  Yoshihiro Kawaoka 4 5 6
Affiliations

Affiliations

  • 1 Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • 2 The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan.
  • 3 Center for Influenza and Respiratory Virus Research, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan.
  • 4 Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. [email protected].
  • 5 The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan. [email protected].
  • 6 Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA. [email protected].
  • # Contributed equally.
PMID: 35705860 DOI: 10.1038/s41564-022-01170-4
Abstract

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the major antigen stimulating the host's protective immune response. Here we assessed the efficacy of therapeutic monoclonal Antibodies (mAbs) against Omicron variant (B.1.1.529) sublineage BA.1 variants in Syrian hamsters. Of the FDA-approved therapeutic mAbs tested (that is, REGN10987/REGN10933, COV2-2196/COV2-2130 and S309), only COV2-2196/COV2-2130 efficiently inhibited BA.1 replication in the lungs of hamsters, and this effect was diminished against a BA.1.1 variant possessing the S-R346K substitution. In addition, treatment of BA.1-infected hamsters with molnupiravir (a SARS-CoV-2 RNA-dependent RNA polymerase inhibitor) or S-217622 (a SARS-CoV-2 protease inhibitor) strongly reduced virus replication in the lungs. These findings suggest that the use of therapeutic mAbs in Omicron-infected patients should be carefully considered due to mutations that affect efficacy, and demonstrate that the Antiviral compounds molnupiravir and S-217622 are effective against Omicron BA.1 variants.

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