Characterization and antiviral susceptibility of SARS-CoV-2 Omicron/BA.2

  • Res Sq. 2022 Feb 24:rs.3.rs-1375091. doi: 10.21203/rs.3.rs-1375091/v1.
Yoshihiro Kawaoka  1 ,  Ryuta Uraki  2 ,  Maki Kiso  3 ,  Shun Iida  4 ,  Masaki Imai  5 ,  Emi Takashita  4 ,  Makoto Kuroda  6 ,  Peter Halfmann  7 ,  Samantha Loeber  1 ,  Tadashi Maemura  8 ,  Seiya Yamayoshi  9 ,  Seiichiro Fujisaki  4 ,  Zhongde Wang  10 ,  Mutsumi Ito  11 ,  Michiko Ujie  12 ,  Kiyoko Iwatsuki-Horimoto  5 ,  Yuri Furusawa  12 ,  Ryan Wright  13 ,  Zhenlu Chong  14 ,  Seiya Ozono  4 ,  Atsuhiro Yasuhara  12 ,  Hiroshi Ueki  15 ,  Yuko Sakai  3 ,  Rong Li  16 ,  Yanan Liu  16 ,  Deanna Larson  17 ,  Michiko Koga  18 ,  Takeya Tsutsumi  19 ,  Eisuke Adachi  18 ,  Makoto Saito  19 ,  Shinya Yamamoto  19 ,  Shohei Matsubara  19 ,  Masao Hagihara  20 ,  Keiko Mitamura  20 ,  Tetsuro Sato  21 ,  Masayuki Hojo  22 ,  Shin-Ichiro Hattori  2 ,  Kenji Maeda  23 ,  Moe Okuda  24 ,  Jurika Murakami  24 ,  Calvin Duong  24 ,  Sucheta Godbole  25 ,  Daniel Douek  26 ,  Shinji Watanabe  4 ,  Norio Ohmagari  27 ,  Hiroshi Yotsuyanagi  5 ,  Michael Diamond  28 ,  Hideki Hasegawa  4 ,  Hiroaki Mitsuya  2 ,  Tadaki Suzuki  4
Affiliations
  • 1. University of Wisconsin-Madison.
  • 2. National Center for Global Health and Medicine Research Institute.
  • 3. Institute of Medical Sciences, University of Tokyo.
  • 4. National Institute of Infectious Diseases.
  • 5. University of Tokyo.
  • 6. University of Wisconsin at Madison.
  • 7. Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA.
  • 8. University of Wisconsin.
  • 9. University Of Tokyo.
  • 10. Utah State University.
  • 11. University of Tokyo, Institute of Medical Science.
  • 12. Division of Virology, Institute of Medical Science, University of Tokyo.
  • 13. Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison.
  • 14. Washington University.
  • 15. The University of Tokyo.
  • 16. Department of Animal Dairy, and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University.
  • 17. Utah State University, College of Agriculture and Applied Sciences.
  • 18. The Institute of Medical Science, the University of Tokyo.
  • 19. Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo.
  • 20. Division of Infection Control, Eiju General Hospital.
  • 21. Disease Control and Prevention Center, National Center for Global Health and Medicine Hospital.
  • 22. Department of Respiratory Medicine, National Center for Global Health and Medicine Hospital.
  • 23. National Center For Global Health and Medicine.
  • 24. Department of Virology, Institute of Medical Science, University of Tokyo.
  • 25. Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health.
  • 26. NIH.
  • 27. Disease Control and Prevention Center, National Center for Global Health and Medicine.
  • 28. Washington University in Saint Louis.
PMID: 35233565 DOI: 10.21203/rs.3.rs-1375091/v1
Abstract

The recent emergence of SARS-CoV-2 Omicron variants possessing large numbers of mutations has raised concerns of decreased effectiveness of current vaccines, therapeutic monoclonal antibodies, and Antiviral drugs for COVID-19 against these variants1,2. While the original Omicron lineage, BA.1, has become dominant in many countries, BA.2 has been detected in at least 67 countries and has become dominant in the Philippines, India, and Denmark. Here, we evaluated the replicative ability and pathogenicity of an authentic infectious BA.2 isolate in immunocompetent and human ACE2 (hACE2)-expressing mice and hamsters. In contrast to recent data with chimeric, recombinant SARS-CoV-2 strains expressing the spike proteins of BA.1 and BA.2 on an ancestral WK-521 backbone3, we observed similar infectivity and pathogenicity in mice and hamsters between BA.2 and BA.1, and less pathogenicity compared to early SARS-CoV-2 strains. We also observed a marked and significant reduction in the neutralizing activity of plasma from COVID-19 convalescent individuals and vaccine recipients against BA.2 compared to ancestral and Delta variant strains. In addition, we found that some therapeutic monoclonal antibodies (REGN10987/REGN10933, COV2-2196/COV2-2130, and S309) and Antiviral drugs (molnupiravir, nirmatrelvir, and S-217622) can restrict viral Infection in the respiratory organs of hamsters infected with BA.2. These findings suggest that the replication and pathogenicity of BA.2 is comparable to that of BA.1 in rodents and that several therapeutic monoclonal antibodies and Antiviral compounds are effective against Omicron/BA.2 variants.

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