Exploring the immune evasion of SARS-CoV-2 variant harboring E484K by molecular dynamics simulations
文献类型：期刊论文
| 作者 | Wu, Leyun1,2; Peng, Cheng1,2; Yang, Yanqing1,2; Shi, Yulong1,2; Zhou, Liping1,2; Xu, Zhijian1,2 ; Zhu, Weiliang1,2
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| 刊名 | BRIEFINGS IN BIOINFORMATICS
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| 出版日期 | 2022-01-17 |
| 卷号 | 23期号:1页码:9 |
| 关键词 | COVID-19 spike E484K antibody MM GBSA |
| ISSN号 | 1467-5463 |
| DOI | 10.1093/bib/bbab383 |
| 通讯作者 | Xu, Zhijian(zjxu@simm.ac.cn) ; Zhu, Weiliang(wlzhu@simm.ac.cn) |
| 英文摘要 | Although the current coronavirus disease 2019 (COVID-19) vaccines have been used worldwide to halt spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the emergence of new SARS-CoV-2 variants with E484K mutation shows significant resistance to the neutralization of vaccine sera. To better understand the resistant mechanism, we calculated the binding affinities of 26 antibodies to wild-type (WT) spike protein and to the protein harboring E484K mutation, respectively. The results showed that most antibodies (similar to 85%) have weaker binding affinities to the E484K mutated spike protein than to the WT, indicating the high risk of immune evasion of the mutated virus from most of current antibodies. Binding free energy decomposition revealed that the residue E484 forms attraction with most antibodies, while the K484 has repulsion from most antibodies, which should be the main reason of the weaker binding affinities of E484K mutant to most antibodies. Impressively, a monoclonal antibody (mAb) combination was found to have much stronger binding affinity with E484K mutant than WT, which may work well against the mutated virus. Based on binding free energy decomposition, we predicted that the mutation of four more residues on receptor-binding domain (RBD) of spike protein, viz., F490, V483, G485 and S494, may have high risk of immune evasion, which we should pay close attention on during the development of new mAb therapeutics. |
| WOS关键词 | RECEPTOR-BINDING ; SPIKE PROTEIN ; FORCE-FIELD ; ANTIBODIES ; CONSTRAINTS ; MECHANICS ; DOMAIN |
| 资助项目 | National Key Research and Development Program of China[2016YFA0502301] ; National Key Research and Development Program of China[2017YFB0202601] ; Natural Science Foundation of Shanghai[21ZR1475600] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Mathematical & Computational Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000763000800014 |
| 出版者 | OXFORD UNIV PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/299845]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Xu, Zhijian; Zhu, Weiliang |
| 作者单位 | 1.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Sch Pharm, 19A Yuquan Rd, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wu, Leyun,Peng, Cheng,Yang, Yanqing,et al. Exploring the immune evasion of SARS-CoV-2 variant harboring E484K by molecular dynamics simulations[J]. BRIEFINGS IN BIOINFORMATICS,2022,23(1):9. |
| APA | Wu, Leyun.,Peng, Cheng.,Yang, Yanqing.,Shi, Yulong.,Zhou, Liping.,...&Zhu, Weiliang.(2022).Exploring the immune evasion of SARS-CoV-2 variant harboring E484K by molecular dynamics simulations.BRIEFINGS IN BIOINFORMATICS,23(1),9. |
| MLA | Wu, Leyun,et al."Exploring the immune evasion of SARS-CoV-2 variant harboring E484K by molecular dynamics simulations".BRIEFINGS IN BIOINFORMATICS 23.1(2022):9. |
入库方式： OAI收割
来源：上海药物研究所
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