Computational analysis of spike protein of SARS-CoV-2 (Omicron variant) for development of peptide-based therapeutics and diagnostics

In the last few years, the worldwide population has suffered from the SARS-CoV-2 pandemic. The WHO dashboard indicated that around 504,079,039 people were infected and 6,204,155 died from COVID-19 caused by different variants of SARS-CoV-2. Recently, a new variant of SARS-CoV-2 (B.1.1.529) was reported by South Africa known as Omicron. The high transmissibility rate and resistance towards available anti-SARS-CoV-2 drugs/vaccines/monoclonal antibodies, make Omicron a variant of concern. Because of various mutations in spike protein, available diagnostic and therapeutic treatments are not reliable. Therefore, the present study explored the development of some therapeutic peptides that can inhibit the SARS-CoV-2 virus interaction with host ACE2 receptors and can also be used for diagnostic purposes. The screened linear B cell epitopes derived from receptor-binding domain of spike protein of Omicron variant were evaluated as peptide inhibitor/vaccine candidates through different bioinformatics tools including molecular docking and simulation to analyze the interaction between Omicron peptide and human ACE2 receptor. Overall, <i>in-silico</i> studies revealed that Omicron peptides OP1-P12, OP14, OP20, OP23, OP24, OP25, OP26, OP27, OP28, OP29, and OP30 have the potential to inhibit Omicron interaction with ACE2 receptor. Moreover, Omicron peptides OP20, OP22, OP23, OP24, OP25, OP26, OP27, and OP30 have shown potential antigenic and immunogenic properties that can be used in design and development vaccines against Omicron. Although the <i>in-silico</i> validation was performed by comparative analysis with the control peptide inhibitor, further validation through wet lab experimentation is required before its use as therapeutic peptides. Communicated by Ramaswamy H. Sarma

近数年来，全球民众饱受严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）大流行之苦。世界卫生组织（WHO）的数据面板显示，累计约504079039人感染由不同SARS-CoV-2变异株引发的新型冠状病毒肺炎（COVID-19），死亡人数达6204155例。近期，南非报告发现SARS-CoV-2的新型变异株（B.1.1.529），即广为人知的奥密克戎（Omicron）。该变异株凭借高传播能力以及对现有抗SARS-CoV-2药物、疫苗、单克隆抗体的耐药性，被列为需关注变异株。由于刺突蛋白存在多种突变，当前可用的诊断与治疗手段可靠性不足。因此，本研究探索开发可抑制SARS-CoV-2与宿主血管紧张素转换酶2（ACE2）受体结合的治疗性多肽，同时可用于诊断用途。本研究通过分子对接、分子模拟等多种生物信息学工具，对从奥密克戎刺突蛋白受体结合域筛选得到的线性B细胞表位进行评估，将其作为多肽抑制剂/疫苗候选物，以分析奥密克戎多肽与人ACE2受体的相互作用。整体而言，计算机模拟（in-silico）研究显示，奥密克戎多肽OP1~OP12、OP14、OP20、OP23、OP24、OP25、OP26、OP27、OP28、OP29及OP30均具备抑制奥密克戎与ACE2受体结合的潜力。此外，奥密克戎多肽OP20、OP22、OP23、OP24、OP25、OP26、OP27及OP30展现出良好的抗原性与免疫原性，可用于奥密克戎疫苗的设计与开发。尽管本研究已通过与对照多肽抑制剂的对比分析完成计算机模拟验证，但该多肽作为治疗性药物应用前，仍需通过湿实验开展进一步验证。由Ramaswamy H. Sarma转交发表。