Gerardi Valeria, Rohaim Mohammed A, Naggar Rania F El, Atasoy Mustafa O, Munir Muhammad
Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YG, UK.
Department of Virology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt.
Vaccines (Basel). 2023 Mar 15;11(3):668. doi: 10.3390/vaccines11030668.
The emergence of the Omicron variant has reinforced the importance of continued SARS-CoV-2 evolution and its possible impact on vaccine effectiveness. Specifically, mutations in the receptor-binding domain (RBD) are critical to comprehend the flexibility and dynamicity of the viral interaction with the human agniotensin-converting enzyme 2 (hACE2) receptor. To this end, we have applied a string of deep structural and genetic analysis tools to map the substitution patterns in the S protein of major Omicron sub-variants (n = 51) with a primary focus on the RBD mutations. This head-to-head comparison of Omicron sub-variants revealed multiple simultaneous mutations that are attributed to antibody escape, and increased affinity and binding to hACE2. Our deep mapping of the substitution matrix indicated a high level of diversity at the N-terminal and RBD domains compared with other regions of the S protein, highlighting the importance of these two domains in a matched vaccination approach. Structural mapping identified highly variable mutations in the up confirmation of the S protein and at sites that critically define the function of the S protein in the virus pathobiology. These substitutional trends offer support in tracking mutations along the evolutionary trajectories of SAR-CoV-2. Collectively, the findings highlight critical areas of mutations across the major Omicron sub-variants and propose several hotspots in the S proteins of SARS-CoV-2 sub-variants to train the future design and development of COVID-19 vaccines.
奥密克戎变种的出现强化了新冠病毒持续进化的重要性及其对疫苗有效性可能产生的影响。具体而言，受体结合域（RBD）中的突变对于理解病毒与人类血管紧张素转换酶2（hACE2）受体相互作用的灵活性和动态性至关重要。为此，我们应用了一系列深入的结构和基因分析工具，以绘制主要奥密克戎子变种（n = 51）S蛋白中的替换模式，主要关注RBD突变。这种对奥密克戎子变种的直接比较揭示了多个同时发生的突变，这些突变归因于抗体逃逸，以及与hACE2的亲和力和结合力增加。我们对替换矩阵的深入绘制表明，与S蛋白的其他区域相比，N端和RBD结构域具有高度的多样性，突出了这两个结构域在匹配疫苗接种方法中的重要性。结构映射确定了S蛋白向上构象中以及在病毒病理生物学中关键定义S蛋白功能的位点处的高度可变突变。这些替换趋势为追踪新冠病毒进化轨迹中的突变提供了支持。总体而言，这些发现突出了主要奥密克戎子变种中突变的关键区域，并提出了新冠病毒子变种S蛋白中的几个热点，以指导未来新冠疫苗的设计和开发。
