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Abstract：
The evolution of new SARS-CoV-2 variants around the globe has made the COVID-19 pandemic more worrisome, further pressuring the health care system and immunity. Novel variations that are unique to the receptor-binding motif (RBM) of the receptor-binding domain (RBD) spike glycoprotein, i. e. L452R-E484Q, may play a different role in the B.1.617 (also known as G/452R.V3) variant\'s pathogenicity and better survival compared to the wild type. Therefore, a thorough analysis is needed to understand the impact of these mutations on binding with host receptor (RBD) and to guide new therapeutics development. In this study, we used structural and biomolecular simulation techniques to explore the impact of specific mutations (L452R-E484Q) in the B.1.617 variant on the binding of RBD to the host receptor ACE2. Our analysis revealed that the B.1.617 variant possesses different dynamic behaviours by altering dynamic-stability, residual flexibility and structural compactness. Moreover, the new variant had altered the bonding network and structural-dynamics properties significantly. MM/GBSA technique was used, which further established the binding differences between the wild type and B.1.617 variant. In conclusion, this study provides a strong impetus to develop novel drugs against the new SARS-CoV-2 variants.
摘要：
新的SARS-CoV-2变种在全球范围内的演变使COVID-19大流行更加令人担忧，进一步向医疗保健系统和免疫力施压。受体结合域（RBD）刺突糖蛋白的受体结合基序（RBM）独特的新变异，i.e.L452R-E484Q,可能在B.1.617（也称为G/452R。与野生型相比，V3）变体的致病性和更好的存活率。因此,需要进行彻底的分析,以了解这些突变对与宿主受体(RBD)结合的影响,并指导新的治疗方法的开发.在这项研究中,我们使用结构和生物分子模拟技术来探索B.1.617变体中特定突变(L452R-E484Q)对RBD与宿主受体ACE2结合的影响.我们的分析表明，B.1.617变体通过改变动态稳定性而具有不同的动态行为，残余的灵活性和结构的紧凑性。此外，新的变体显著改变了键合网络和结构动力学特性。采用MM/GBSA技术，这进一步确立了野生型和B.1.617变体之间的结合差异。总之,这项研究为开发针对新的SARS-CoV-2变种的新药提供了强大的动力。
