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Structure-Based Optimization of One Neutralizing Antibody against SARS-CoV-2 Variants Bearing the L452R Mutation

文献类型：期刊论文

作者Chen, Yamin5,6; Zha, Jialu4; Xu, Shiqi2,3,5; Shao, Jiang5; Liu, Xiaoshan5,6; Li, Dianfan4; Zhang, Xiaoming1,5,6
刊名VIRUSES-BASEL
出版日期2024-04-01
卷号16期号:4页码:9
关键词COVID-19 neutralizing antibody structure-based antibody optimization L452R mutation
DOI10.3390/v16040566
通讯作者Li, Dianfan(dianfan.li@sibcb.ac.cn) ; Zhang, Xiaoming(xmzhang@ips.ac.cn)
英文摘要Neutralizing antibodies (nAbs) play an important role against SARS-CoV-2 infections. Previously, we have reported one potent receptor binding domain (RBD)-binding nAb Ab08 against the SARS-CoV-2 prototype and a panel of variants, but Ab08 showed much less efficacy against the variants harboring the L452R mutation. To overcome the antibody escape caused by the L452R mutation, we generated several structure-based Ab08 derivatives. One derivative, Ab08-K99E, displayed the mostly enhanced neutralizing potency against the Delta pseudovirus bearing the L452R mutation compared to the Ab08 and other derivatives. Ab08-K99E also showed improved neutralizing effects against the prototype, Omicron BA.1, and Omicron BA.4/5 pseudoviruses. In addition, compared to the original Ab08, Ab08-K99E exhibited high binding properties and affinities to the RBDs of the prototype, Delta, and Omicron BA.4/5 variants. Altogether, our findings report an optimized nAb, Ab08-K99E, against SARS-CoV-2 variants and demonstrate structure-based optimization as an effective way for antibody development against pathogens.
资助项目National Key Research and Development Program of China
WOS研究方向Virology
语种英语
WOS记录号WOS:001210429200001
出版者MDPI
源URL[http://119.78.100.183/handle/2S10ELR8/310870]  
专题新药研究国家重点实验室
通讯作者Li, Dianfan; Zhang, Xiaoming
作者单位1.Shanghai Sci Tech Inno Ctr Infect & Immun, Shanghai 200052, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201210, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201210, Peoples R China
4.Shanghai Inst Biochem & Cell Biol, Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai 200031, Peoples R China
5.Shanghai Inst Immun & Infect, Chinese Acad Sci, Key Lab Immune Response & Immunotherapy, Shanghai 200031, Peoples R China
6.Soochow Univ, Suzhou Med Coll, Suzhou 215123, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Yamin,Zha, Jialu,Xu, Shiqi,et al. Structure-Based Optimization of One Neutralizing Antibody against SARS-CoV-2 Variants Bearing the L452R Mutation[J]. VIRUSES-BASEL,2024,16(4):9.
APA Chen, Yamin.,Zha, Jialu.,Xu, Shiqi.,Shao, Jiang.,Liu, Xiaoshan.,...&Zhang, Xiaoming.(2024).Structure-Based Optimization of One Neutralizing Antibody against SARS-CoV-2 Variants Bearing the L452R Mutation.VIRUSES-BASEL,16(4),9.
MLA Chen, Yamin,et al."Structure-Based Optimization of One Neutralizing Antibody against SARS-CoV-2 Variants Bearing the L452R Mutation".VIRUSES-BASEL 16.4(2024):9.

入库方式： OAI收割

来源：上海药物研究所

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