Fig.S1. muscleORF1ab 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（betacoronavirus）科，主要通过有症状与无症状传播的人际接触途径进行传播。自其出现以来，尽管学界已开展多项研究，但目前尚无经证实有效的药物或疫苗治疗手段。因此，研发潜在的多亚单位疫苗已成为当务之急。本研究旨在从SARS-CoV-2的全套蛋白中筛选全球保守的表位（epitope），因目前对这些蛋白的免疫原性尚未形成明确认知。研究团队借助多种计算工具，对经由抗原加工与提呈通路三大核心阶段产生的潜在免疫原性广谱表位进行排序，生成优先级列表。此外，本次分析还获得了多项有价值的研究发现：其中最为关键的一点是，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此类独特表位，T细胞过度活化所触发的强免疫应答可能引发细胞因子风暴与免疫病理损伤，进而大幅降低人体存活概率。此类表位在完成体外（in vitro）验证后，需以多亚单位表位疫苗的形式递送至人体，以规避上述免疫病理风险。