Fig. S7. muscleORF7a 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 via 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 in vitro, 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）已成为本世纪最致命的病原体之一，引发了史无前例的大流行。该病毒隶属于β冠状病毒属（betacoronavirus），主要通过有症状与无症状传播实现人际接触扩散。自其出现以来，尽管学界已开展多项探索，但目前尚无获批的药物或疫苗治疗方案。因此，开发潜在的多亚单位疫苗已是当务之急。本研究尝试从SARS-CoV-2的全套蛋白中筛选全球保守性表位，因目前对这些蛋白的免疫原性尚无明确认知。研究团队借助多样化的计算工具，对经过抗原加工与呈递通路全部三个核心阶段所产生的潜在免疫原性、通用性表位进行了排序，并生成优先级列表。此外，本次分析还获得了多项有价值的研究见解。其中最为关键的一项发现为：该病原体的所有蛋白均携带独特表位，因此仅靶向少数几种病毒蛋白，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细胞过度活化所触发的强烈免疫反应可能会引发细胞因子风暴与免疫病理损伤，进而大幅降低人类的存活几率。因此，这些表位在经过体外（in vitro）验证后，需要以多亚单位表位疫苗的形式递送至人体，以规避此类免疫病理反应。