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PLoS Pathog
. 2023 May 17;19(5):e1011123.
doi: 10.1371/journal.ppat.1011123. Online ahead of print. Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2
Yong Ma 1 , Pengbin Li 1 , Yunqi Hu 1 , Tianyi Qiu 2 , Lixiang Wang 3 , Hongjie Lu 1 , Kexin Lv 1 , Mengxin Xu 1 , Jiaxin Zhuang 4 , Xue Liu 4 , Suhua He 5 , Bing He 1 , Shuning Liu 1 , Lin Liu 1 , Yuanyuan Wang 1 , Xinyu Yue 1 , Yanmei Zhai 1 , Wanyu Luo 1 , Haoting Mai 1 , Yu Kuang 1 , Shifeng Chen 6 , Feng Ye 6 , Na Zhou 6 , Wenjing Zhao 4 , Jun Chen 3 , Shoudeng Chen 5 , Xiaoli Xiong 7 , Mang Shi 4 , Ji-An Pan 4 , Yao-Qing Chen 1 8
Affiliations
SARS-CoV Spike (S) protein shares considerable homology with SARS-CoV-2 S, especially in the conserved S2 subunit (S2). S protein mediates coronavirus receptor binding and membrane fusion, and the latter activity can greatly influence coronavirus infection. We observed that SARS-CoV S is less effective in inducing membrane fusion compared with SARS-CoV-2 S. We identify that S813T mutation is sufficient in S2 interfering with the cleavage of SARS-CoV-2 S by TMPRSS2, reducing spike fusogenicity and pseudoparticle entry. Conversely, the mutation of T813S in SARS-CoV S increased fusion ability and viral replication. Our data suggested that residue 813 in the S was critical for the proteolytic activation, and the change from threonine to Serine at 813 position might be an evolutionary feature adopted by SARS-2-related viruses. This finding deepened the understanding of Spike fusogenicity and could provide a new perspective for exploring Sarbecovirus' evolution.
. 2023 May 17;19(5):e1011123.
doi: 10.1371/journal.ppat.1011123. Online ahead of print. Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2
Yong Ma 1 , Pengbin Li 1 , Yunqi Hu 1 , Tianyi Qiu 2 , Lixiang Wang 3 , Hongjie Lu 1 , Kexin Lv 1 , Mengxin Xu 1 , Jiaxin Zhuang 4 , Xue Liu 4 , Suhua He 5 , Bing He 1 , Shuning Liu 1 , Lin Liu 1 , Yuanyuan Wang 1 , Xinyu Yue 1 , Yanmei Zhai 1 , Wanyu Luo 1 , Haoting Mai 1 , Yu Kuang 1 , Shifeng Chen 6 , Feng Ye 6 , Na Zhou 6 , Wenjing Zhao 4 , Jun Chen 3 , Shoudeng Chen 5 , Xiaoli Xiong 7 , Mang Shi 4 , Ji-An Pan 4 , Yao-Qing Chen 1 8
Affiliations
- PMID: 37196033
- DOI: 10.1371/journal.ppat.1011123
SARS-CoV Spike (S) protein shares considerable homology with SARS-CoV-2 S, especially in the conserved S2 subunit (S2). S protein mediates coronavirus receptor binding and membrane fusion, and the latter activity can greatly influence coronavirus infection. We observed that SARS-CoV S is less effective in inducing membrane fusion compared with SARS-CoV-2 S. We identify that S813T mutation is sufficient in S2 interfering with the cleavage of SARS-CoV-2 S by TMPRSS2, reducing spike fusogenicity and pseudoparticle entry. Conversely, the mutation of T813S in SARS-CoV S increased fusion ability and viral replication. Our data suggested that residue 813 in the S was critical for the proteolytic activation, and the change from threonine to Serine at 813 position might be an evolutionary feature adopted by SARS-2-related viruses. This finding deepened the understanding of Spike fusogenicity and could provide a new perspective for exploring Sarbecovirus' evolution.