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Fusogenicity of SARS-CoV-2 BA.2.86 subvariant and its sensitivity to the prokaryotic recombinant EK1 peptide

作者:Lijue Wang, Fanke Jiao, Hanxiao Jiang, Yitao Yang, Ziqi Huang, Qian Wang, Wei Xu, Yun Zhu, Shuai Xia, Shibo Jiang, Lu Lu · 发表于:Cell Discovery · 年份:2024 · DOI:10.1038/s41421-023-00631-2 · 被引用次数:14 · 研究领域:SARS-CoV-2 and COVID-19 Research、SARS-CoV-2 detection and testing、Viral gastroenteritis research and epidemiology

BA.2.86, a novel SARS-CoV-2 Omicron subvariant, has emerged along with widespread concerns since the number of mutations in its S protein exceeds that of other Omicron subvariants (Fig. 1a ). On August 18, 2023, the World Health Organization formally classified BA.2.86 as a variant under monitoring (VUM) 1 . Notably, numerous studies have reported that BA.2.86 has evaded humoral immunity induced by both inactivated and mRNA SARS-CoV-2 vaccines, as well as COVID-19 convalescent plasma 2 , 3 . However, in comparison to previous dominant SARS-CoV-2 Omicron subvariants, the fusogenicity of BA.2.86 and its sensitivity to coronavirus fusion and replication inhibitors have yet to be systematically evaluated. Fig. 1: Fusogenicity of BA.2.86 S protein and the antiviral efficacy of reEK1. a Distinct S protein mutational profile of the Omicron subvariant BA.2.86. b Representative images of cell-cell fusion mediated by 293 T/WT(D614G)-S, BA.1-S, BA.2-S, BA.2.75-S, BA.2.86-S, XBB.1.5-S, EG.5-S, or negative control after coculture for 8 h. Scale bars, 150 µm. c Rate of fusion mediated by WT(D614G)-S, BA.1-S, BA.2-S, BA.2.75-S, BA.2.86-S, XBB.1.5-S and EG.5-S proteins on Calu-3 cells after coculture for 2, 4, 8 and 24 h. As compared with the BA.2.86 group, asterisks indicate significant differences (* P < 0.05; ** P < 0.01; *** P < 0.001, **** P < 0.0001). d Alteration of fusion capacity mediated by S939F mutation in the HR1 region. e Effect of S939F mutation on the prefusion state of S pro...