PLoS Pathogens (May 2023)

Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2.

  • Yong Ma,
  • Pengbin Li,
  • Yunqi Hu,
  • Tianyi Qiu,
  • Lixiang Wang,
  • Hongjie Lu,
  • Kexin Lv,
  • Mengxin Xu,
  • Jiaxin Zhuang,
  • Xue Liu,
  • Suhua He,
  • Bing He,
  • Shuning Liu,
  • Lin Liu,
  • Yuanyuan Wang,
  • Xinyu Yue,
  • Yanmei Zhai,
  • Wanyu Luo,
  • Haoting Mai,
  • Yu Kuang,
  • Shifeng Chen,
  • Feng Ye,
  • Na Zhou,
  • Wenjing Zhao,
  • Jun Chen,
  • Shoudeng Chen,
  • Xiaoli Xiong,
  • Mang Shi,
  • Ji-An Pan,
  • Yao-Qing Chen

DOI
https://doi.org/10.1371/journal.ppat.1011123
Journal volume & issue
Vol. 19, no. 5
p. e1011123

Abstract

Read online

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.