Center of Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Suzhou Institute of Systems Medicine, Suzhou, China.
Front Cell Infect Microbiol. 2021 Oct 13;11:720357. doi: 10.3389/fcimb.2021.720357. eCollection 2021.
SARS-coronavirus 2 (SARS-CoV-2), pathogen of coronavirus disease 2019 (COVID-19), is constantly evolving to adapt to the host and evade antiviral immunity. The newly emerging variants N501Y.V1 (B.1.1.7) and N501Y.V2 (B.1.351), first reported in the United Kingdom and South Africa respectively, raised concerns due to the unusually rapid global spread. The mutations in spike (S) protein may contribute to the rapid spread of these variants. Here, with a vesicular stomatitis virus (VSV)-based pseudotype system, we demonstrated that the pseudovirus bearing N501Y.V2 S protein has higher infection efficiency than pseudovirus with wildtype (WT) and D614G S protein. Moreover, pseudovirus with N501Y.V1 or N501Y.V2 S protein has better thermal stability than WT and D614G, suggesting these mutations of variants may increase the stability of SARS-CoV-2 S protein and virion. However, the pseudovirus bearing N501Y.V1 or N501Y.V2 S protein has similar sensitivity to inhibitors of protease and endocytosis with WT and D614G. These findings could be of value in preventing the spread of virus and developing drugs for emerging SARS-CoV-2 variants.
严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)是 2019 年冠状病毒病(COVID-19)的病原体,它不断进化以适应宿主并逃避抗病毒免疫。新出现的 N501Y.V1(B.1.1.7)和 N501Y.V2(B.1.351)变异株最初分别在英国和南非报告,由于其异常迅速的全球传播而引起关注。刺突(S)蛋白中的突变可能有助于这些变异株的快速传播。在这里,我们使用水疱性口炎病毒(VSV)为基础的假型系统,证明携带 N501Y.V2 S 蛋白的假病毒具有比野生型(WT)和 D614G S 蛋白更高的感染效率。此外,携带 N501Y.V1 或 N501Y.V2 S 蛋白的假病毒比 WT 和 D614G 具有更好的热稳定性,这表明这些变异株的突变可能增加了 SARS-CoV-2 S 蛋白和病毒粒子的稳定性。然而,携带 N501Y.V1 或 N501Y.V2 S 蛋白的假病毒对 WT 和 D614G 的蛋白酶和内吞抑制剂的敏感性相似。这些发现可能对预防病毒传播和开发针对新兴 SARS-CoV-2 变异株的药物具有价值。