■为了通过多亚单位疫苗设计来对抗SARS-CoV-2,在使用全基因组和免疫组的研究中,ORF10,位于基因组的3'末端,显示独特的功能。它与其他生物体中的任何已知蛋白质都没有同源性,包括SARS-CoV.据观察,其核苷酸序列在全球范围内的SARS-CoV-2基因组中100%相同,即使在B.1.1.529(Omicron)的最新VoCs和VoIs中,B.1.617(Delta),B.1.1.7(Alpha),B.1.351(Beta),和P.1(伽玛)谱系,在致命变体的进化过程中暗示了它的恒定性质。
■SARS-CoV-2ORF10的结构和功能及其在病毒进化中可能发挥的作用尚不清楚。这项研究的目的是预测其结构,函数,并了解这种致命病毒的免疫发病机制中突变和可能增强的免疫反应的基础上的进化动力学。
■序列分析,进行了从头算结构建模和对蛋白质关键区域中可能取代的影响的理解。对病毒T细胞表位和主要锚定残基突变进行了分析,以了解其作为可能增强免疫应答和随后的免疫发病机制的分子在进化中可能发挥的作用。
■很少观察到氨基酸取代突变,很可能是由于核糖体移码,这些突变可能不会损害其功能。由于观察到ORF10是一种表达的蛋白质,从头算结构模型表明,它主要包含α-螺旋区,可能是ER靶向的膜小蛋白。分析整个蛋白质组,据观察,ORF10在最多数量的可能混杂和免疫原性CTL表位中存在,特别是30个混杂表位中的11个和这11个免疫原性CTL表位中的9个。这些表位的反应性T细胞已在独立研究中被发现。这些表位大多位于其结构的α-螺旋区,并且这些表位中初级锚定残基的取代突变不影响免疫原性。它的保守核苷酸序列在整个进化和多样化的病毒到几个变体是一个难题,有待解决。
■根据其顺序,结构,和表位定位,结论是,它的功能可能类似于那些在医学应用中用于增强免疫反应的微型蛋白。由于即使在SARS-CoV-2基因组首次测序几年后,核苷酸序列仍具有完整的保守性,它提出了一个独特的难题需要解决,鉴于全球人群中出现的变异的进化动态。
UNASSIGNED: In an effort to combat SARS-CoV-2 through multi-subunit vaccine design, during studies using whole genome and immunome,
ORF10, located at the 3\' end of the genome, displayed unique features. It showed no homology to any known protein in other organisms, including SARS-CoV. It was observed that its nucleotide sequence is 100% identical in the SARS-CoV-2 genomes sourced worldwide, even in the recent-most VoCs and VoIs of B.1.1.529 (Omicron), B.1.617 (Delta), B.1.1.7 (Alpha), B.1.351 (Beta), and P.1 (Gamma) lineages, implicating its constant nature throughout the evolution of deadly variants.
UNASSIGNED: The structure and function of SARS-CoV-2
ORF10 and the role it may play in the viral evolution is yet to be understood clearly. The aim of this study is to predict its structure, function, and understand evolutionary dynamics on the basis of mutations and likely heightened immune responses in the immunopathogenesis of this deadly virus.
UNASSIGNED: Sequence analysis, ab-initio structure modeling and an understanding of the impact of likely substitutions in key regions of protein was carried out. Analyses of viral T cell epitopes and primary anchor residue mutations was done to understand the role it may play in the evolution as a molecule with likely enhanced immune response and consequent immunopathogenesis.
UNASSIGNED: Few amino acid substitution mutations are observed, most probably due to the ribosomal frameshifting, and these mutations may not be detrimental to its functioning. As
ORF10 is observed to be an expressed protein, ab-initio structure modeling shows that it comprises mainly an α-helical region and maybe an ER-targeted membrane mini-protein. Analyzing the whole proteome, it is observed that
ORF10 presents amongst the highest number of likely promiscuous and immunogenic CTL epitopes, specifically 11 out of 30 promiscuous ones and 9 out of these 11, immunogenic CTL epitopes. Reactive T cells to these epitopes have been uncovered in independent studies. Majority of these epitopes are located on the α-helix region of its structure, and the substitution mutations of primary anchor residues in these epitopes do not affect immunogenicity. Its conserved nucleotide sequence throughout the evolution and diversification of virus into several variants is a puzzle yet to be solved.
UNASSIGNED: On the basis of its sequence, structure, and epitope mapping, it is concluded that it may function like those mini-proteins used to boost immune responses in medical applications. Due to the complete nucleotide sequence conservation even a few years after SARS-CoV-2 genome was first sequenced, it poses a unique puzzle to be solved, in view of the evolutionary dynamics of variants emerging in the populations worldwide.