TY - JOUR
T1 - The spike receptor-binding motif G496S substitution determines the replication fitness of SARS-CoV-2 Omicron sublineage
AU - Liang, Ronghui
AU - Ye, Zi Wei
AU - Ong, Chon Phin
AU - Qin, Zhenzhi
AU - Xie, Yubin
AU - Fan, Yilan
AU - Tang, Kaiming
AU - Poon, Vincent Kwok Man
AU - Chan, Chris Chung Sing
AU - Yang, Xiaomeng
AU - Cao, Hehe
AU - Wang, Kun
AU - Sun, Haoran
AU - Hu, Bodan
AU - Cai, Jian Piao
AU - Luo, Cuiting
AU - Chik, Kenn Ka Heng
AU - Chu, Hin
AU - Zheng, Yi
AU - Yuen, Kwok Yung
AU - Chan, Jasper Fuk Woo
AU - Jin, Dong Yan
AU - Yuan, Shuofeng
N1 - Publisher Copyright:
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - COVID-19
KW - G496S
KW - Omicron BA.1
KW - Omicron BA.2
KW - fitness
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U2 - 10.1080/22221751.2022.2111977
DO - 10.1080/22221751.2022.2111977
M3 - Article
C2 - 35943779
AN - SCOPUS:85137136500
SN - 2222-1751
VL - 11
SP - 2093
EP - 2101
JO - Emerging Microbes and Infections
JF - Emerging Microbes and Infections
IS - 1
ER -