Lubinski Bailey, Jaimes Javier A, Whittaker Gary R
Graduate Field of Biological & Biomedical Sciences, Cornell University, Ithaca NY, 14853, USA.
Department of Microbiology & Immunology, College of Veterinary Medicine, Cornell University, Ithaca NY, 14853, USA.
bioRxiv. 2022 Jul 26:2022.04.20.488969. doi: 10.1101/2022.04.20.488969.
The ability of SARS-CoV-2 to be primed for viral entry by the host cell protease furin has become one of the most investigated of the numerous transmission and pathogenicity features of the virus. SARS-CoV-2 The variant B.1.1.529 (Omicron) emerged in late 2020 and has continued to evolve and is now present in several distinct sub-variants. Here, we analyzed the "furin cleavage site" of the spike protein of SARS-CoV-2 B.1.1.529 (Omicron variant) , to assess the role of two key mutations (spike, N679K and P681H) that are common across all subvariants compared to the ancestral B.1 virus and other notable lineages. We observed significantly increased intrinsic cleavability with furin compared to an original B lineage virus (Wuhan-Hu1), as well as to two variants, B.1.1.7 (Alpha) and B.1.617 (Delta) that subsequently had wide circulation. Increased furin-mediated cleavage was attributed to the N679K mutation, which lies outside the conventional furin binding pocket. Our findings suggest that B.1.1.529 (Omicron variant) has gained genetic features linked to intrinsic furin cleavability, in line with its evolution within the population as the COVID-19 pandemic has proceeded.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）通过宿主细胞蛋白酶弗林蛋白酶启动病毒进入的能力，已成为该病毒众多传播和致病性特征中研究最多的特征之一。SARS-CoV-2的B.1.1.529变异株（奥密克戎）于2020年末出现，并持续进化，目前存在多个不同的亚变体。在此，我们分析了SARS-CoV-2 B.1.1.529（奥密克戎变异株）刺突蛋白的“弗林蛋白酶切割位点”，以评估与原始B.1病毒及其他显著谱系相比，在所有亚变体中均存在的两个关键突变（刺突蛋白的N679K和P681H）的作用。我们观察到，与原始B谱系病毒（武汉-胡1）以及随后广泛传播的两个变体B.1.1.7（阿尔法）和B.1.617（德尔塔）相比，弗林蛋白酶对其内在切割能力显著增强。弗林蛋白酶介导的切割增加归因于位于传统弗林蛋白酶结合口袋之外的N679K突变。我们的研究结果表明，随着新冠疫情的发展，B.1.1.529（奥密克戎变异株）获得了与弗林蛋白酶内在切割能力相关的遗传特征，这与其在人群中的进化一致。
