Virological characteristics of the SARS-CoV-2 Omicron BA.2 subvariants, including BA.4 and BA.5

After the global spread of the SARS-CoV-2 Omicron BA.2, some BA.2 subvariants, including BA.2.9.1, BA.2.11, BA.2.12.1, BA.4, and BA.5, emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these BA.2 subvariants are greater than that of the origina...

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Published in:Cell 2022-10, Vol.185 (21), p.3992-4007.e16
Main Authors: Kimura, Izumi, Yamasoba, Daichi, Tamura, Tomokazu, Nao, Naganori, Suzuki, Tateki, Oda, Yoshitaka, Mitoma, Shuya, Ito, Jumpei, Nasser, Hesham, Zahradnik, Jiri, Uriu, Keiya, Fujita, Shigeru, Kosugi, Yusuke, Wang, Lei, Tsuda, Masumi, Kishimoto, Mai, Ito, Hayato, Suzuki, Rigel, Shimizu, Ryo, Begum, MST Monira, Yoshimatsu, Kumiko, Kimura, Kanako Terakado, Sasaki, Jiei, Sasaki-Tabata, Kaori, Yamamoto, Yuki, Nagamoto, Tetsuharu, Kanamune, Jun, Kobiyama, Kouji, Asakura, Hiroyuki, Nagashima, Mami, Sadamasu, Kenji, Yoshimura, Kazuhisa, Shirakawa, Kotaro, Takaori-Kondo, Akifumi, Kuramochi, Jin, Schreiber, Gideon, Ishii, Ken J., Hashiguchi, Takao, Ikeda, Terumasa, Saito, Akatsuki, Fukuhara, Takasuke, Tanaka, Shinya, Matsuno, Keita, Sato, Kei
Format: Article
Language:English
Subjects:
Angiotensin-Converting Enzyme 2
Antibodies, Viral
BA.2
BA.2.12.1
BA.4
BA.5
COVID-19
Humans
immune resistance
Omicron
pathogenicity
Peptidyl-Dipeptidase A - genetics
Peptidyl-Dipeptidase A - metabolism
SARS-CoV-2
Spike Glycoprotein, Coronavirus - genetics
Spike Glycoprotein, Coronavirus - metabolism
transmissibility
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Summary:After the global spread of the SARS-CoV-2 Omicron BA.2, some BA.2 subvariants, including BA.2.9.1, BA.2.11, BA.2.12.1, BA.4, and BA.5, emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these BA.2 subvariants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1/2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. We further provided the structure of the BA.4/5 spike receptor-binding domain that binds to human ACE2 and considered how the substitutions in the BA.4/5 spike play roles in ACE2 binding and immune evasion. Moreover, experiments using hamsters suggested that BA.4/5 is more pathogenic than BA.2. Our multiscale investigations suggest that the risk of BA.2 subvariants, particularly BA.4/5, to global health is greater than that of original BA.2. [Display omitted] •BA.4/5 is resistant to immunity induced by BA.1 and BA.2 infections•Substitutions in the BA.4/5 spike contribute to immune escape and ACE2 binding strength•BA.4/5 is more fusogenic and more efficiently spread in human lung cells than BA.2•BA.4/5 spike-bearing virus is more pathogenic than BA.2 spike-bearing virus The SARS-CoV-2 Omicron variants BA.4 and BA.5 are currently causing infections and COVID-19 morbidities worldwide. Compared with the earlier variant BA.2, BA.4/5 shows more efficient replication and is more fusogenic. Structural views as well as in vivo studies in hamsters explain the antibody evasion and increased pathogenicity of BA.4/5 over BA.2.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2022.09.018