Laboratório de Planejamento e Desenvolvimento de Fármacos, Universidade Federal do Pará, Rua Augusto Correa S/N, Belém, PA, Brazil.
Sci Rep. 2022 May 20;12(1):8540. doi: 10.1038/s41598-022-12479-9.
The severe acute respiratory syndrome (SARS) coronavirus 2 (CoV-2) variant Omicron spread more rapid than the other variants of SARS-CoV-2 virus. Mutations on the Spike (S) protein receptor-binding domain (RBD) are critical for the antibody resistance and infectivity of the SARS-CoV-2 variants. In this study, we have used accelerated molecular dynamics (aMD) simulations and free energy calculations to present a systematic analysis of the affinity and conformational dynamics along with the interactions that drive the binding between Spike protein RBD and human angiotensin-converting enzyme 2 (ACE2) receptor. We evaluate the impacts of the key mutation that occur in the RBDs Omicron and other variants in the binding with the human ACE2 receptor. The results show that S protein Omicron has stronger binding to the ACE2 than other variants. The evaluation of the decomposition energy per residue shows the mutations N440K, T478K, Q493R and Q498R observed in Spike protein of SARS-CoV-2 provided a stabilization effect for the interaction between the SARS-CoV-2 RBD and ACE2. Overall, the results demonstrate that faster spreading of SARS-CoV-2 Omicron may be correlated with binding affinity of S protein RBD to ACE2 and mutations of uncharged residues to positively charged residues such as Lys and Arg in key positions in the RBD.
严重急性呼吸系统综合症 (SARS) 冠状病毒 2 (CoV-2) 的奥密克戎变异株比 SARS-CoV-2 病毒的其他变异株传播得更快。棘突（S）蛋白受体结合域（RBD）上的突变对于 SARS-CoV-2 变异株的抗体抗性和感染力至关重要。在这项研究中，我们使用加速分子动力学（aMD）模拟和自由能计算，对棘突蛋白 RBD 与人类血管紧张素转化酶 2（ACE2）受体之间的亲和力和构象动力学以及驱动结合的相互作用进行了系统分析。我们评估了 RBD 中发生的关键突变对奥密克戎和其他变异株与人类 ACE2 受体结合的影响。结果表明，S 蛋白奥密克戎与 ACE2 的结合比其他变异株更强。对每个残基分解能的评估表明，在 SARS-CoV-2 棘突蛋白中观察到的突变 N440K、T478K、Q493R 和 Q498R 对 SARS-CoV-2 RBD 和 ACE2 之间的相互作用提供了稳定作用。总的来说，结果表明，SARS-CoV-2 奥密克戎传播速度更快可能与 S 蛋白 RBD 与 ACE2 的结合亲和力以及 RBD 关键位置中性残基突变为带正电荷的残基如赖氨酸和精氨酸有关。
