Emergence of RBD mutations in circulating SARS-CoV-2 strains enhancing the structural stability and human ACE2 receptor affinity of the spike protein

BioRxiv : the Preprint Server for Biology
Junxian OuQiwei Zhang

Abstract

A novel coronavirus SARS-CoV-2 is associated with the current global pandemic of Coronavirus Disease 2019 (COVID-19). Spike protein receptor-binding domain (RBD) of SARS-CoV-2 is the critical determinant of viral tropism and infectivity. To investigate whether the mutations in the RBD have altered the receptor binding affinity and whether these strains are selected to be more infectious, we analyzed and assessed the binding dynamics between the mutant SARS-CoV-2 RBDs to date and the human ACE2 receptor. Among 1609 genomes of global SARS-CoV-2 strains, 32 RBD mutants were identified and clustered into 9 mutant types under high positive selection pressure. Three mutant types that emerged in Wuhan, Shenzhen, Hong Kong, and France, displayed higher human ACE2 affinity, and probably higher infectivity. This is due to the enhanced structural stabilization of the RBD beta-sheet scaffold. Five France isolates and one Hong Kong isolate shared the same RBD mutation (V367F). 13 V483A mutants and seven G476S mutants were also identified from the U.S.A. This suggested they originated as novel sub-lineages. The enhancement of the binding affinity of the mutant type (V367F) was further validated by the receptor-ligand binding ELISA assay. The...Continue Reading

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