Rutgers Cancer Institute of New Jersey, Newark, NJ 07101, USA.
Division of Cancer Biology, Department of Radiation Oncology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.
Mol Biol Evol. 2022 May 3;39(5). doi: 10.1093/molbev/msac091.
Evaluation of immunogenic epitopes for universal vaccine development in the face of ongoing SARS-CoV-2 evolution remains a challenge. Herein, we investigate the genetic and structural conservation of an immunogenically relevant epitope (C662-C671) of spike (S) protein across SARS-CoV-2 variants to determine its potential utility as a broad-spectrum vaccine candidate against coronavirus diseases. Comparative sequence analysis, structural assessment, and molecular dynamics simulations of C662-C671 epitope were performed. Mathematical tools were employed to determine its mutational cost. We found that the amino acid sequence of C662-C671 epitope is entirely conserved across the observed major variants of SARS-CoV-2 in addition to SARS-CoV. Its conformation and accessibility are predicted to be conserved, even in the highly mutated Omicron variant. Costly mutational rate in the context of energy expenditure in genome replication and translation can explain this strict conservation. These observations may herald an approach to developing vaccine candidates for universal protection against emergent variants of coronavirus.
面对 SARS-CoV-2 的持续进化，评估用于通用疫苗开发的免疫原表位仍然是一个挑战。在此，我们研究了刺突（S）蛋白中一个免疫相关表位（C662-C671）在 SARS-CoV-2 变异体中的遗传和结构保守性，以确定其作为针对冠状病毒病的广谱疫苗候选物的潜在用途。对 C662-C671 表位进行了比较序列分析、结构评估和分子动力学模拟。使用数学工具来确定其突变代价。我们发现，C662-C671 表位的氨基酸序列在除 SARS-CoV 之外的 SARS-CoV-2 主要观察到的变异体中是完全保守的。即使在高度突变的奥密克戎变异体中，其构象和可及性预计也是保守的。在基因组复制和翻译的能量消耗方面的高代价突变率可以解释这种严格的保守性。这些观察结果可能预示着开发针对冠状病毒新兴变异体的通用保护疫苗候选物的方法。
