Cueno Marni E, Imai Kenichi
Department of Microbiology, Nihon University School of Dentistry, Tokyo, Japan.
Front Genet. 2021 Oct 22;12:773726. doi: 10.3389/fgene.2021.773726. eCollection 2021.
Coronavirus disease 2019 (COVID-19) pandemic has been attributed to SARS-CoV-2 (SARS2) and, consequently, SARS2 has evolved into multiple SARS2 variants driving subsequent waves of infections. In particular, variants of concern (VOC) were identified to have both increased transmissibility and virulence ascribable to mutational changes occurring within the spike protein resulting to modifications in the protein structural orientation which in-turn may affect viral pathogenesis. However, this was never fully elucidated. Here, we generated spike models of endemic HCoVs (HCoV 229E, HCoV OC43, HCoV NL63, HCoV HKU1, SARS CoV, MERS CoV), original SARS2, and VOC (alpha, beta, gamma, delta). Model quality check, structural superimposition, and structural comparison based on RMSD values, TM scores, and contact mapping were all performed. We found that: 1) structural comparison between the original SARS2 and VOC whole spike protein model have minor structural differences (TM > 0.98); 2) the whole VOC spike models putatively have higher structural similarity (TM > 0.70) to spike models from endemic HCoVs coming from the same phylogenetic cluster; 3) original SARS2 S1-CTD and S1-NTD models are structurally comparable to VOC S1-CTD (TM = 1.0) and S1-NTD (TM > 0.96); and 4) endemic HCoV S1-CTD and S1-NTD models are structurally comparable to VOC S1-CTD (TM > 0.70) and S1-NTD (TM > 0.70) models belonging to the same phylogenetic cluster. Overall, we propose that structural similarities (possibly ascribable to similar conformational epitopes) may help determine immune cross-reactivity, whereas, structural differences (possibly associated with varying conformational epitopes) may lead to viral infection (either reinfection or breakthrough infection).
2019年冠状病毒病（COVID-19）大流行被归因于严重急性呼吸综合征冠状病毒2（SARS-CoV-2，简称SARS2），因此，SARS2已演变成多个SARS2变体，引发了后续的感染浪潮。特别是，令人担忧的变体（VOC）被确定具有更高的传播性和毒力，这归因于刺突蛋白内发生的突变变化，导致蛋白质结构取向发生改变，进而可能影响病毒发病机制。然而，这一点从未得到充分阐明。在此，我们构建了地方性人冠状病毒（HCoV 229E、HCoV OC43、HCoV NL63、HCoV HKU1、SARS-CoV、MERS-CoV）、原始SARS2和VOC（阿尔法、贝塔、伽马、德尔塔）的刺突模型。进行了模型质量检查、结构叠加以及基于均方根偏差值、TM分数和接触图谱的结构比较。我们发现：1）原始SARS2和VOC全刺突蛋白模型之间的结构比较存在微小结构差异（TM>0.98）；2）整个VOC刺突模型与来自同一系统发育簇的地方性HCoV刺突模型具有更高的结构相似性（TM>0.70）；3）原始SARS2的S1-CTD和S1-NTD模型在结构上与VOC的S1-CTD（TM = 1.0）和S1-NTD（TM>0.96）相当；4）地方性HCoV的S1-CTD和S1-NTD模型在结构上与属于同一系统发育簇的VOC的S1-CTD（TM>0.70）和S1-NTD（TM>0.70）模型相当。总体而言，我们提出结构相似性（可能归因于相似的构象表位）可能有助于确定免疫交叉反应性，而结构差异（可能与不同的构象表位相关）可能导致病毒感染（再次感染或突破性感染）。
