Fig. S8. muscleORF8 from Designing of cytotoxic and helper T cell epitope map provides insights into the highly contagious nature of the pandemic novel coronavirus SARS-CoV-2

Novel coronavirus, SARS-CoV-2, has emerged as one of the deadliest pathogens of this century, creating an unprecedented pandemic. Belonging to the betacoronavirus family, it primarily spreads through human contact <i>via</i> symptomatic and asymptomatic transmission. Despite several attempts since it emerged, there is no known treatment in the form of drugs or vaccines. Hence, work on developing a potential multi-subunit vaccine is the need of the hour. In this study, attempts have been made to find globally conserved epitopes from the entire set of SARS-CoV-2 proteins as there is as yet, no clear information on the immunogenicity of these proteins. Using diverse computational tools, a ranked list of probable immunogenic, promiscuous epitopes generated through all the three main stages of antigen processing and presentation pathways has been prioritized. Moreover, several useful insights were gleaned during these analyses. One of the most important insights is that all of the proteins in this pathogen present unique epitopes, so that the targeting of a few specific viral proteins is not likely to result in an effective immune response in humans. Due to the presence of these unique epitopes in all of the SARS-CoV-2 proteins, stronger immune responses generated by T cell hyperactivation may lead to cytokine storm and immunopathology and consequently, remote chances of human survival. These epitopes, after due validation <i>in vitro</i>, may thus need to be presented to the human body in that form of multi-subunit epitope-based vaccine that avoids such immunopathologies.

新型冠状病毒（SARS-CoV-2）已成为本世纪致死性最强的病原体之一，引发了史无前例的全球大流行。该病毒隶属于乙型冠状病毒属（betacoronavirus），主要通过人际接触传播，涵盖有症状感染与无症状感染两种途径。自其出现以来，尽管学界已开展诸多探索，但目前尚未发现可用于该疾病的药物或疫苗治疗手段。因此，研发潜在的多亚单位疫苗已是当务之急。
本研究旨在从SARS-CoV-2的全部蛋白组中筛选出全球保守的表位（epitope），因目前学界对这些蛋白的免疫原性仍缺乏明确认知。研究团队借助多样化的计算工具，对经抗原加工提呈通路（antigen processing and presentation pathways）三大核心阶段所产生的潜在免疫原性、泛特异性表位（promiscuous epitope）进行排序，并优先筛选出高可信度的候选列表。此外，本次分析还获得了多项极具价值的研究发现：其中最为关键的结论为，该病原体的所有蛋白均携带独特表位，因此仅靶向少数特定病毒蛋白，难以在人体中引发有效的免疫应答。
由于SARS-CoV-2的所有蛋白中均存在这类独特表位，T细胞过度活化所介导的强效免疫应答可能引发细胞因子风暴（cytokine storm）与免疫病理损伤（immunopathology），进而大幅降低人类的存活概率。因此，这些表位在经过体外（in vitro）验证后，需要以规避上述免疫病理风险的多亚单位表位疫苗形式递送至人体。