Gupta Jyoti, Malik Md Zubbair, Chaturvedi Maya, Mishra Mohit, Mishra Surbhi Kriti, Grover Abhinav, Ray Ashwini Kumar, Chaturvedi Rupesh
New Delhi, 110067 India School of Biotechnology, Jawaharlal Nehru University.
Dasman, 15462 Kuwait Department of Genetics and Bioinformatics, Dasman Diabetes Institute.
Virusdisease. 2023 May 24;34(2):1-19. doi: 10.1007/s13337-023-00820-3.
The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is related with the COVID-19 pandemic. Recent spike protein variations have had an effect on the transmission of the virus. In addition to ACE-2, spike proteins can employ DC-SIGN and its analogous receptor, DC-SIGNR, for host evasion. Spike variations in the DC-SIGN interaction region and role of DC-SIGN in immune evasion have not been well defined. To understand the spike protein variations and their binding mode, phylogenetic analysis of the complete GISAID (Global Initiative for Sharing Avian Influenza Data) data of the SARS-CoV-2 spike protein was considered. In addition, an in silico knockout network evaluation of the SARS-CoV-2 single-cell transcriptome was conducted to determine the key role of DC-SIGN/R in immunological dysregulation. Within the DC-SIGN-interacting region of the SARS-CoV spike protein, the spike protein of SARS-CoV-2 displayed remarkable similarity to the SARS-CoV spike protein. Surprisingly, the phylogenetic analysis revealed that the SARS-CoV-2's spike exhibited significantly diverse variants in the DC-SIGN interaction domain, which altered the frequency of these variants. The variation within the DC-SIGN-interacting domain of spike proteins affected the binding of a limited number of variants with DC-SIGN and DC-SIGNR and affected their evolution. MMGBSA binding free energies evaluation differed for variants from those of the wild type, suggesting the influence of substitution mutations on the interaction pattern. In silico knockout network analysis of the single-cell transcriptome of Bronchoalveolar Lavage and peripheral blood mononuclear cells revealed that SARS-CoV-2 altered DC-SIGN/R signaling. Early surveillance of diverse SARS-CoV-2 strains could preclude a worsening of the pandemic and facilitate the development of an optimum vaccine against variations. The spike Receptor Binding Domain genetic variants are thought to boost SARS CoV-2 immune evasion, resulting in its higher longevity.
The online version contains supplementary material available at 10.1007/s13337-023-00820-3.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）与新型冠状病毒肺炎大流行有关。近期刺突蛋白变异对病毒传播产生了影响。除了血管紧张素转换酶2（ACE-2）外，刺突蛋白还可利用树突状细胞特异性细胞间黏附分子3抓取非整合素（DC-SIGN）及其类似受体DC-SIGNR来逃避免疫。刺突蛋白在DC-SIGN相互作用区域的变异以及DC-SIGN在免疫逃逸中的作用尚未明确。为了解刺突蛋白变异及其结合模式，我们对严重急性呼吸综合征冠状病毒2刺突蛋白的完整全球共享禽流感数据倡议（GISAID）数据进行了系统发育分析。此外，还对严重急性呼吸综合征冠状病毒2单细胞转录组进行了计算机敲除网络评估，以确定DC-SIGN/R在免疫失调中的关键作用。在严重急性呼吸综合征冠状病毒刺突蛋白的DC-SIGN相互作用区域内，严重急性呼吸综合征冠状病毒2的刺突蛋白与严重急性呼吸综合征冠状病毒的刺突蛋白表现出显著相似性。令人惊讶的是，系统发育分析表明，严重急性呼吸综合征冠状病毒2的刺突在DC-SIGN相互作用域表现出明显不同的变异，这改变了这些变异的频率。刺突蛋白DC-SIGN相互作用域内的变异影响了少数变异与DC-SIGN和DC-SIGNR的结合，并影响了它们的进化。分子力学广义Born表面面积结合自由能评估显示变异体与野生型不同，表明取代突变对相互作用模式有影响。对支气管肺泡灌洗和外周血单核细胞单细胞转录组的计算机敲除网络分析表明，严重急性呼吸综合征冠状病毒2改变了DC-SIGN/R信号传导。对不同严重急性呼吸综合征冠状病毒2毒株的早期监测可以防止大流行恶化，并有助于开发针对变异的最佳疫苗。刺突受体结合域基因变异被认为增强了严重急性呼吸综合征冠状病毒2的免疫逃逸能力，从而使其具有更长的存活时间。
在线版本包含可在10.1007/s13337-023-00820-3获取的补充材料。
