Chemo-genomics Research Unit, Department of Biochemistry, Adekunle Ajasin University, Akungba-Akoko, Ondo State, Nigeria.
Bio-Computing Research Unit, Mols and Sims, Ado-Ekiti, Ekiti State, Nigeria.
J Comput Chem. 2020 Sep 15;41(24):2158-2161. doi: 10.1002/jcc.26383. Epub 2020 Jul 21.
D614G spike glycoprotein (sgp) mutation in rapidly spreading severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) is associated with enhanced fitness and higher transmissibility in new cases of COVID-19 but the underlying mechanism is unknown. Here, using atomistic simulation, a plausible mechanism has been delineated. In G614 sgp but not wild type, increased D(G)614-T859 Cα-distance within 65 ns is interpreted as S1/S2 protomer dissociation. Overall, ACE2-binding, post-fusion core, open-state and sub-optimal antibody-binding conformations were preferentially sampled by the G614 mutant, but not wild type. Furthermore, in the wild type, only one of the three sgp chains has optimal communication route between residue 614 and the receptor-binding domain (RBD); whereas, two of the three chains communicated directly in G614 mutant. These data provide evidence that D614G sgp mutant is more available for receptor binding, cellular invasion and reduced antibody interaction; thus, providing framework for enhanced fitness and higher transmissibility in D614G SARS-COV-2 mutant.
D614G 刺突糖蛋白（sgp）突变与 COVID-19 新病例中增强的适应性和更高的传染性相关，但潜在机制尚不清楚。在这里，我们使用原子模拟方法，阐述了一个合理的机制。在 G614 sgp 中，但在野生型中没有，在 65ns 内增加的 D(G)614-T859 Cα 距离被解释为 S1/S2 原聚体解离。总体而言，ACE2 结合、融合后核心、开放状态和次优的抗体结合构象优先被 G614 突变体而不是野生型采样。此外，在野生型中，只有三个 sgp 链中的一个具有 614 位残基和受体结合域（RBD）之间的最佳通讯途径；而在 G614 突变体中，有两条链直接通讯。这些数据提供了证据表明，D614G sgp 突变体更易于与受体结合、细胞入侵和减少抗体相互作用；因此，为 D614G SARS-COV-2 突变体增强的适应性和更高的传染性提供了框架。
