Molecular characterization of interactions between the D614G variant of SARS-CoV-2 S-protein and neutralizing antibodies: A computational approach.
Molecular characterization of interactions between the D614G variant of SARS-CoV-2 S-protein and neutralizing antibodies: A computational approach.
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DOI：
10.1016/j.meegid.2021.104815
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发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Asiedu SO
中科院分区：
文献类型：
--
作者：
Kwarteng A;Asiedu E;Sylverken AA;Larbi A;Sakyi SA;Asiedu SO
SARS-CoV-2 S蛋白的D 614 G变体于2020年初出现，并迅速成为欧洲及其周边地区的主要流行毒株。该变体的特征在于较高的病毒载量，其与疾病严重程度无关，较高的病毒体掺入，以及通过ACE-2和TMPRSS 2的高细胞进入。先前的冠状病毒株和目前的SARS-CoV-2已经证明选择突变是逃避免疫反应的机制。在这项研究中，我们使用分子动力学模拟和MM-PBSA结合能分析，以提供深入了解的D 614 G S-蛋白在分子水平上的行为，并描述这种变体的中和机制。我们的研究结果表明，D 614 G S-蛋白采用不同的构象动力学是偏向于开放状态的构象比野生型S-蛋白的封闭状态的构象。残基特异性的氨基酸的灵活性和结构域特异性的RMSD的变化表明，突变引起的RBD的变构构象变化。对S蛋白和中和抗体之间的相互作用能的评估表明，突变可能会增强、减少或不影响中和相互作用，这取决于中和抗体，特别是如果它靶向RBD。这项研究的结果揭示了D 614 G S蛋白在分子水平上的行为，并提供了这种变体的中和机制的一瞥。
The D614G variant of SARS-CoV-2 S-protein emerged in early 2020 and quickly became the dominant circulating strain in Europe and its environs. The variant was characterized by the higher viral load, which is not associated with disease severity, higher incorporation into the virion, and high cell entry via ACE-2 and TMPRSS2. Previous strains of the coronavirus and the current SARS-CoV-2 have demonstrated the selection of mutations as a mechanism of escaping immune responses. In this study, we used molecular dynamics simulation and MM-PBSA binding energy analysis to provide insights into the behaviour of the D614G S-protein at the molecular level and describe the neutralization mechanism of this variant. Our results show that the D614G S-protein adopts distinct conformational dynamics which is skewed towards the open-state conformation more than the closed-state conformation of the wild-type S-protein. Residue-specific variation of amino acid flexibility and domain-specific RMSD suggest that the mutation causes an allosteric conformational change in the RBD. Evaluation of the interaction energies between the S-protein and neutralizing antibodies show that the mutation may enhance, reduce or not affect the neutralizing interactions depending on the neutralizing antibody, especially if it targets the RBD. The results of this study have shed insights into the behaviour of the D614G S-protein at the molecular level and provided a glimpse of the neutralization mechanism of this variant.
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影响因子：
7.7
作者：
Weisblum Y;Schmidt F;Zhang F;DaSilva J;Poston D;Lorenzi JC;Muecksch F;Rutkowska M;Hoffmann HH;Michailidis E;Gaebler C;Agudelo M;Cho A;Wang Z;Gazumyan A;Cipolla M;Luchsinger L;Hillyer CD;Caskey M;Robbiani DF;Rice CM;Nussenzweig MC;Hatziioannou T;Bieniasz PD
通讯作者：
Bieniasz PD
影响因子：
3.5
作者：
Deller MC;Rupp B
通讯作者：
Rupp B
影响因子：
3
作者：
Vanommeslaeghe, K.;Hatcher, E.;Acharya, C.;Kundu, S.;Zhong, S.;Shim, J.;Darian, E.;Guvench, O.;Lopes, P.;Vorobyov, I.;MacKerell, A. D., Jr.
通讯作者：
MacKerell, A. D., Jr.
影响因子：
4.6
作者：
Isabel, Sandra;Grana-Miraglia, Lucia;Poutanen, Susan M.
通讯作者：
Poutanen, Susan M.
影响因子：
30.3
作者：
Weissman D;Alameh MG;de Silva T;Collini P;Hornsby H;Brown R;LaBranche CC;Edwards RJ;Sutherland L;Santra S;Mansouri K;Gobeil S;McDanal C;Pardi N;Hengartner N;Lin PJC;Tam Y;Shaw PA;Lewis MG;Boesler C;Şahin U;Acharya P;Haynes BF;Korber B;Montefiori DC
通讯作者：
Montefiori DC