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Evolutionary and structural analysis elucidates mutations on SARS-CoV2 spike protein with altered human ACE2 binding affinity.
Biochem Biophys Res Commun. 2021 01 01; 534:374-380.BB

Abstract

The recognition of ACE2 by the receptor-binding domain (RBD) of spike protein mediates host cell entry. The objective of the work is to identify SARS-CoV2 spike variants that emerged during the pandemic and evaluate their binding affinity with ACE2. Evolutionary analysis of 2178 SARS-CoV2 genomes identifies RBD variants that are under selection bias. The binding efficacy of these RBD variants to the ACE2 has been analyzed by using protein-protein docking and binding free energy calculations. Pan-proteomic analysis reveals 113 mutations among them 33 are parsimonious. Evolutionary analysis reveals five RBD variants A348T, V367F, G476S, V483A, and S494P are under strong positive selection bias. Variations at these sites alter the ACE2 binding affinity. A348T, G476S, and V483A variants display reduced affinity to ACE2 in comparison to the Wuhan SARS-CoV2 spike protein. While the V367F and S494P population variants display a higher binding affinity towards human ACE2. Reorientation of several crucial residues at the RBD-ACE2 interface facilitates additional hydrogen bond formation for the V367F variant which enhances the binding energy during ACE2 recognition. On the other hand, the enhanced binding affinity of S494P is attributed to strong interfacial complementarity between the RBD and ACE2.

Authors+Show Affiliations

Amity Institute of Biotechnology, Amity University, Kolkata, 700135, India. Electronic address: sandipanchakraborty.13@gmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33272568

Citation

Chakraborty, Sandipan. "Evolutionary and Structural Analysis Elucidates Mutations On SARS-CoV2 Spike Protein With Altered Human ACE2 Binding Affinity." Biochemical and Biophysical Research Communications, vol. 534, 2021, pp. 374-380.
Chakraborty S. Evolutionary and structural analysis elucidates mutations on SARS-CoV2 spike protein with altered human ACE2 binding affinity. Biochem Biophys Res Commun. 2021;534:374-380.
Chakraborty, S. (2021). Evolutionary and structural analysis elucidates mutations on SARS-CoV2 spike protein with altered human ACE2 binding affinity. Biochemical and Biophysical Research Communications, 534, 374-380. https://doi.org/10.1016/j.bbrc.2020.11.075
Chakraborty S. Evolutionary and Structural Analysis Elucidates Mutations On SARS-CoV2 Spike Protein With Altered Human ACE2 Binding Affinity. Biochem Biophys Res Commun. 2021 01 1;534:374-380. PubMed PMID: 33272568.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evolutionary and structural analysis elucidates mutations on SARS-CoV2 spike protein with altered human ACE2 binding affinity. A1 - Chakraborty,Sandipan, Y1 - 2020/11/28/ PY - 2020/11/17/received PY - 2020/11/19/accepted PY - 2020/12/5/pubmed PY - 2021/4/20/medline PY - 2020/12/4/entrez KW - ACE2 KW - Binding free energy KW - Population variants KW - Selection KW - Spike glycoprotein SP - 374 EP - 380 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 534 N2 - The recognition of ACE2 by the receptor-binding domain (RBD) of spike protein mediates host cell entry. The objective of the work is to identify SARS-CoV2 spike variants that emerged during the pandemic and evaluate their binding affinity with ACE2. Evolutionary analysis of 2178 SARS-CoV2 genomes identifies RBD variants that are under selection bias. The binding efficacy of these RBD variants to the ACE2 has been analyzed by using protein-protein docking and binding free energy calculations. Pan-proteomic analysis reveals 113 mutations among them 33 are parsimonious. Evolutionary analysis reveals five RBD variants A348T, V367F, G476S, V483A, and S494P are under strong positive selection bias. Variations at these sites alter the ACE2 binding affinity. A348T, G476S, and V483A variants display reduced affinity to ACE2 in comparison to the Wuhan SARS-CoV2 spike protein. While the V367F and S494P population variants display a higher binding affinity towards human ACE2. Reorientation of several crucial residues at the RBD-ACE2 interface facilitates additional hydrogen bond formation for the V367F variant which enhances the binding energy during ACE2 recognition. On the other hand, the enhanced binding affinity of S494P is attributed to strong interfacial complementarity between the RBD and ACE2. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/33272568/Evolutionary_and_structural_analysis_elucidates_mutations_on_SARS_CoV2_spike_protein_with_altered_human_ACE2_binding_affinity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(20)32120-3 DB - PRIME DP - Unbound Medicine ER -