Abstract

The replication and pathogenicity of SARS-CoV-2 Omicron BA.2 are comparable to that of BA.1 in experimental animal models. However, BA.2 has rapidly emerged to overtake BA.1 to become the predominant circulating SARS-CoV-2 variant worldwide. Here, we compared the replication fitness of BA.1 and BA.2 in cell culture and in the Syrian hamster model of COVID-19. Using a reverse genetics approach, we found that the BA.1-specific spike mutation G496S compromises its replication fitness, which may contribute to BA.1 being outcompeted by BA.2 in the real world. Additionally, the BA.1-unique G496S substitution confers differentiated sensitivity to therapeutic monoclonal antibodies, which partially recapitulates the immunoevasive phenotype of BA.1 and BA.2. In summary, our study identified G496S as an important determinant during the evolutionary trajectory of SARS-CoV-2.

Details

Title
The spike receptor-binding motif G496S substitution determines the replication fitness of SARS-CoV-2 Omicron sublineage
Author
Liang, Ronghui 1 ; Zi-Wei, Ye 1   VIAFID ORCID Logo  ; Ong, Chon Phin 2 ; Qin, Zhenzhi 1 ; Xie, Yubin 1 ; Fan, Yilan 2 ; Tang, Kaiming 1 ; Poon, Vincent Kwok-Man 3 ; Chris Chung-Sing Chan 3 ; Yang, Xiaomeng 1 ; Cao, Hehe 1 ; Wang, Kun 1 ; Sun, Haoran 4 ; Hu, Bodan 1 ; Jian-Piao Cai 1 ; Luo, Cuiting 1 ; Kenn Ka-Heng Chik 5 ; Chu, Hin 6   VIAFID ORCID Logo  ; Zheng, Yi 7 ; Kwok-Yung, Yuen 8   VIAFID ORCID Logo  ; Jasper Fuk-Woo Chan 8   VIAFID ORCID Logo  ; Dong-Yan, Jin 9   VIAFID ORCID Logo  ; Yuan, Shuofeng 6   VIAFID ORCID Logo 

1  State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of China 
2  School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of China 
3  State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of China; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Shatin, Hong Kong Special Administrative Region, People’s Republic of China 
4  Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, People’s Republic of China 
5  State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of China; Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, People’s Republic of China 
6  State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of China; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Shatin, Hong Kong Special Administrative Region, People’s Republic of China; Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, People’s Republic of China 
7  Key Laboratory of Infection and Immunity of Shandong Province, Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China 
8  State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of China; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Shatin, Hong Kong Special Administrative Region, People’s Republic of China; Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, People’s Republic of China; Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of China; Academician Workstation of Hainan Province, Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University, Haikou, People’s Republic of China; Guangzhou Laboratory, Guangdong Province, People’s Republic of China 
9  School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People’s Republic of China; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Shatin, Hong Kong Special Administrative Region, People’s Republic of China; Guangzhou Laboratory, Guangdong Province, People’s Republic of China 
Pages
2093-2101
Publication year
2022
Publication date
Dec 2022
Publisher
Taylor & Francis Ltd.
e-ISSN
22221751
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1080/22221751.2022.2111977
ProQuest document ID
2748034984
Copyright
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.