Department of Anatomy, Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 117594, Singapore.
Viruses. 2023 May 18;15(5):1193. doi: 10.3390/v15051193.
Of various SARS-CoV-2 variants, some have drawn special concern or interest because of their heightened disease threat. The mutability of individual SARS-CoV-2 genes/proteins presumably varies. The present study quantified gene/protein mutations in 13 major SARS-CoV-2 variants of concern/interest, and analyzed viral protein antigenicity using bioinformatics. The results from 187 carefully perused genome clones showed significantly higher mean percent mutations in the spike, ORF8, nucleocapsid, and NSP6 than in other viral proteins. The ORF8 and spike proteins also tolerated higher maximal percent mutations. The omicron variant presented more percent mutations in the NSP6 and structural proteins, whereas the delta featured more in the ORF7a. Omicron subvariant BA.2 exhibited more mutations in ORF6, and omicron BA.4 had more in NSP1, ORF6, and ORF7b, relative to omicron BA.1. Delta subvariants AY.4 and AY.5 bore more mutations in ORF7b and ORF8 than delta B.1.617.2. Predicted antigen ratios of SARS-CoV-2 proteins significantly vary (range: 38-88%). To overcome SARS-CoV-2 immune evasion, the relatively conserved, potentially immunogenic NSP4, NSP13, NSP14, membrane, and ORF3a viral proteins may serve as more suitable targets for molecular vaccines or therapeutics than the mutation-prone NSP6, spike, ORF8, or nucleocapsid protein. Further investigation into distinct mutations of the variants/subvariants may help understand SARS-CoV-2 pathogenesis.
在各种 SARS-CoV-2 变体中，有些因其更高的疾病威胁而引起特别关注或兴趣。单个 SARS-CoV-2 基因/蛋白质的变异性可能有所不同。本研究定量分析了 13 种主要关注/感兴趣的 SARS-CoV-2 变体中的基因/蛋白质突变，并使用生物信息学分析了病毒蛋白抗原性。对 187 个精心检测的基因组克隆的研究结果表明，刺突蛋白、ORF8、核衣壳和 NSP6 的平均突变百分比明显高于其他病毒蛋白。ORF8 和刺突蛋白也能耐受更高的最大突变百分比。奥密克戎变体在 NSP6 和结构蛋白中表现出更高的突变百分比，而德尔塔在 ORF7a 中更为明显。奥密克戎亚变体 BA.2 在 ORF6 中表现出更多的突变，奥密克戎 BA.4 在 NSP1、ORF6 和 ORF7b 中表现出更多的突变，与奥密克戎 BA.1 相比。德尔塔亚变体 AY.4 和 AY.5 在 ORF7b 和 ORF8 中比德尔塔 B.1.617.2 有更多的突变。SARS-CoV-2 蛋白的预测抗原比显著不同（范围：38-88%）。为了克服 SARS-CoV-2 的免疫逃避，相对保守的、潜在免疫原性的 NSP4、NSP13、NSP14、膜和 ORF3a 病毒蛋白可能比易突变的 NSP6、刺突蛋白、ORF8 或核衣壳蛋白更适合作为分子疫苗或治疗药物的靶标。对变体/亚变体的不同突变的进一步研究可能有助于了解 SARS-CoV-2 的发病机制。
