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Dynamics prediction of emerging notable spike protein mutations in SARS-CoV-2 implies a need for updated vaccines
Biochimie ( IF 3.9 ) Pub Date : 2021-09-08 , DOI: 10.1016/j.biochi.2021.08.011
Walid Al-Zyoud 1 , Hazem Haddad 2
Affiliation  

The spike protein of SARS-CoV-2 plays a crucial role in binding with the human cell surface, which causes its pathogenicity. This study aimed to predict molecular dynamics change of emerging variants in the spike protein. In this study, several structural biology tools, such as SuperPose, were utilized to study spike protein structures' thermodynamics, superimposition, and the spike protein disulphide bonds. This questions the current vaccines efficacies that were based on the Nextstrain clade 19A that first documented in Wuhan and lacks any variants. The prediction results of this study have exhibited the stabilizing role of the globally dominant variant, the D614G; clade 20A, and other variants in addition to their role in increasing the flexibility of the spike protein of the virus. The SuperPose findings have revealed a conformational change impact of D614G in allowing the polybasic Furin cleavage site (682RRAR↓S686) to be closer to the receptor-binding domain (RBD) and hence more exposed to cleavage. The presence of D614G in any clade or subclade, such as 20A, B.1.1.7 (20I/501Y.V1) or Alpha, B.1.351 (20H/501Y.V2) or Beta, P.1 (20J/501Y.V3) or Gamma, B.1.617.2 (21A/478K.V1) or Delta, has increased its stability and flexibility and unified the superimposition among all clades which might impact the virus ability to escape the antibodies neutralization by changing the antigenicity drift of the protein three-dimensional (3D) structure from the wild type clade 19A; this is in agreement with previous study. In conclusion, a new design for the current vaccines to include at least the mutation D614G is immediately needed.



中文翻译:

SARS-CoV-2 中出现的显着刺突蛋白突变的动态预测意味着需要更新疫苗

SARS-CoV-2的刺突蛋白在与人体细胞表面的结合中发挥着至关重要的作用,从而导致其致病性。这项研究旨在预测刺突蛋白中新出现的变体的分子动力学变化。在这项研究中,使用了几种结构生物学工具(例如 SuperPose)来研究刺突蛋白结构的热力学、叠加和刺突蛋白二硫键。这对当前基于 Nextstrain clade 19A 的疫苗功效提出了质疑,该菌株首次在武汉记录,且不存在任何变异。本研究的预测结果展示了全球优势变体D614G的稳定作用;进化枝 20A 和其他变体除了在增加病毒刺突蛋白的灵活性方面发挥作用外。SuperPose 的研究结果揭示了 D614G 的构象变化影响,使多元弗林蛋白酶切割位点 ( 682 RRAR↓S 686 ) 更接近受体结合域 (RBD),因此更容易受到切割。D614G 在任何进化枝或亚进化枝中的存在,例如 20A、B.1.1.7 (20I/501Y.V1) 或 Alpha、B.1.351 (20H/501Y.V2) 或 Beta、P.1 (20J/501Y.V2)。 V3) 或 Gamma、B.1.617.2 (21A/478K.V1) 或 Delta,增加了其稳定性和灵活性,并统一了所有进化枝之间的叠加,这可能通过改变抗体的抗原性漂移来影响病毒逃避抗体中和的能力来自野生型分支 19A 的蛋白质三维 (3D) 结构;这与之前的研究一致。总之,立即需要对当前疫苗进行新设计,至少包含 D614G 突变。

更新日期:2021-09-14
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