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

• Published in: Nature (London) 2022-07, Vol.607 (7917), p.119-127
• Main Authors: Uraki, Ryuta, Kiso, Maki, Iida, Shun, Imai, Masaki, Takashita, Emi, Kuroda, Makoto, Halfmann, Peter J., Loeber, Samantha, Maemura, Tadashi, Yamayoshi, Seiya, Fujisaki, Seiichiro, Wang, Zhongde, Ito, Mutsumi, Ujie, Michiko, Iwatsuki-Horimoto, Kiyoko, Furusawa, Yuri, Wright, Ryan, Chong, Zhenlu, Ozono, Seiya, Yasuhara, Atsuhiro, Ueki, Hiroshi, Sakai-Tagawa, Yuko, Li, Rong, Liu, Yanan, Larson, Deanna, Koga, Michiko, Tsutsumi, Takeya, Adachi, Eisuke, Saito, Makoto, Yamamoto, Shinya, Hagihara, Masao, Mitamura, Keiko, Sato, Tetsuro, Hojo, Masayuki, Hattori, Shin-ichiro, Maeda, Kenji, Valdez, Riccardo, Okuda, Moe, Murakami, Jurika, Duong, Calvin, Godbole, Sucheta, Douek, Daniel C., Maeda, Ken, Watanabe, Shinji, Gordon, Aubree, Ohmagari, Norio, Yotsuyanagi, Hiroshi, Diamond, Michael S., Hasegawa, Hideki, Mitsuya, Hiroaki, Suzuki, Tadaki, Kawaoka, Yoshihiro
• Format: Article
• Language: English
• Subjects: 13; 13/21; 59; 631/326/22/1295; 631/326/596/4130; 64; 64/110; 64/60; ACE2; Airway management; Amino acids; Angiotensin-converting enzyme 2; Animals; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antibodies, Neutralizing - pharmacology; Antibodies, Neutralizing - therapeutic use; Antibodies, Viral - pharmacology; Antibodies, Viral - therapeutic use; Antigens; Antiviral agents; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Antiviral drugs; Chemokines; Coronaviruses; COVID-19; COVID-19 - genetics; COVID-19 - immunology; COVID-19 - virology; COVID-19 Drug Treatment; COVID-19 vaccines; Cricetinae; Cytidine - analogs & derivatives; Cytokines; Drug Combinations; Drugs; Hamsters; Humanities and Social Sciences; Hydroxylamines; Immunization; Immunocompetence; Indazoles; Infections; Infectivity; Lactams; Leucine; Lungs; Mice; Monoclonal antibodies; multidisciplinary; Mutation; Nitriles; Organs; Pathogenicity; Pathogens; Proline; Proteins; Respiratory organs; Rodents; SARS-CoV-2 - drug effects; SARS-CoV-2 - genetics; SARS-CoV-2 - pathogenicity; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - genetics; Transgenic animals; Triazines; Triazoles; Vaccines; Viral diseases; Viral infections; Viruses
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-022-04856-1

The recent emergence of SARS-CoV-2 Omicron (B.1.1.529 lineage) variants possessing numerous mutations has raised concerns of decreased effectiveness of current vaccines, therapeutic monoclonal antibodies and antiviral drugs for COVID-19 against these variants 1 , 2 . The original Omicron lineage, BA.1, prevailed in many countries, but more recently, BA.2 has become dominant in at least 68 countries 3 . Here we evaluated the replicative ability and pathogenicity of authentic infectious BA.2 isolates in immunocompetent and human ACE2-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 backbone 4 , we observed similar infectivity and pathogenicity in mice and hamsters for BA.2 and BA.1, and less pathogenicity compared with early SARS-CoV-2 strains. We also observed a marked and significant reduction in the neutralizing activity of plasma from individuals who had recovered from COVID-19 and vaccine recipients against BA.2 compared to ancestral and Delta variant strains. In addition, we found that some therapeutic monoclonal antibodies (REGN10987 plus REGN10933, COV2-2196 plus COV2-2130, and S309) and antiviral drugs (molnupiravir, nirmatrelvir and S-217622) can restrict viral infection in the respiratory organs of BA.2-infected hamsters. These findings suggest that the replication and pathogenicity of BA.2 is similar to that of BA.1 in rodents and that several therapeutic monoclonal antibodies and antiviral compounds are effective against Omicron BA.2 variants. Isolates of authentic SARS-CoV-2 variants BA.1 and BA.2 exhibit similar infectivity and pathogenicity and show susceptibility to neutralizing therapeutic antibodies and antiviral compounds in mouse and hamster models.