Fig. S6. muscleNS6 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）已跻身本世纪最致命病原体之列，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），主要通过有症状与无症状传播的人际接触途径实现传播。自该病毒出现以来，尽管已有诸多探索尝试，但目前尚未发现以药物或疫苗形式存在的有效治疗手段，因此研发潜在的多亚单位疫苗已是当下重中之重。本研究从SARS-CoV-2的全部蛋白组中筛选全球保守的表位（epitope），因学界目前对这些蛋白的免疫原性仍缺乏明确认知。研究借助多样化的计算工具，对经抗原加工与呈递通路三大核心阶段产生的潜在免疫原性兼嗜性表位进行排序，生成优先级列表。此外，本次分析过程中还获得多项有价值的发现，其中最为关键的一项为：该病原体的所有蛋白均携带有独特表位，仅靶向少数特定病毒蛋白难以在人体中引发有效免疫应答。由于SARS-CoV-2的所有蛋白中均存在这类独特表位，T细胞过度激活所引发的过强免疫应答可能导致细胞因子风暴与免疫病理损伤，进而大幅降低人体存活几率。这些表位在完成体外（in vitro）验证后，需以多亚单位表位疫苗的形式递送于人体，从而规避上述免疫病理风险。