201. Molecular insights into receptor binding of recent emerging SARS-CoV-2 variants
- Author
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Chengpeng Qiao, Anqi Zheng, Jing Li, Sheng Niu, Qihui Wang, Yanfang Zhang, Yuqin Zhang, Mengsu Yang, Qing Wang, Niu Huang, Chao Su, Pengcheng Han, Zengyuan Zhang, Yu Hu, Heecheol Cho, Hanyi Liao, Weiwei Li, Jianxun Qi, Xiaoyu Rong, Xin Zhao, Chongzhi Bai, Qian Chen, Jinghua Yan, and George F. Gao
- Subjects
viruses ,Science ,Mutant ,General Physics and Astronomy ,Virus Attachment ,Computational biology ,Spodoptera ,Molecular Dynamics Simulation ,medicine.disease_cause ,Crystallography, X-Ray ,General Biochemistry, Genetics and Molecular Biology ,Article ,law.invention ,law ,Cell Line, Tumor ,medicine ,Sf9 Cells ,Animals ,Humans ,Protein Interaction Domains and Motifs ,Amino Acid Sequence ,Receptor ,Beta (finance) ,Peptide sequence ,X-ray crystallography ,Mutation ,Multidisciplinary ,biology ,SARS-CoV-2 ,HEK 293 cells ,COVID-19 ,General Chemistry ,Viral proteins ,Surface Plasmon Resonance ,Virus Internalization ,biology.organism_classification ,Recombinant Proteins ,HEK293 Cells ,Spike Glycoprotein, Coronavirus ,Recombinant DNA ,Angiotensin-Converting Enzyme 2 ,hormones, hormone substitutes, and hormone antagonists - Abstract
Multiple SARS-CoV-2 variants of concern (VOCs) have been emerging and some have been linked to an increase in case numbers globally. However, there is yet a lack of understanding of the molecular basis for the interactions between the human ACE2 (hACE2) receptor and these VOCs. Here we examined several VOCs including Alpha, Beta, and Gamma, and demonstrate that five variants receptor-binding domain (RBD) increased binding affinity for hACE2, and four variants pseudoviruses increased entry into susceptible cells. Crystal structures of hACE2-RBD complexes help identify the key residues facilitating changes in hACE2 binding affinity. Additionally, soluble hACE2 protein efficiently prevent most of the variants pseudoviruses. Our findings provide important molecular information and may help the development of novel therapeutic and prophylactic agents targeting these emerging mutants., The SARS-CoV-2 spike (S) protein mediates viral entry by binding of its receptor-binding domain (RBD) to the human angiotensin-converting enzyme 2 (ACE2) receptor and mutations of the S protein may have a great impact on virus transmissibility. Here, the authors characterize the interactions of six different SARS-CoV-2 RBD variants among them Alpha, Beta and Gamma and present crystal structures of these ACE2-RBD complexes.
- Published
- 2021