V367F Mutation in SARS-CoV-2 Spike RBD Emerging during the Early Transmission Phase Enhances Viral Infectivity through Increased Human ACE2 Receptor Binding Affinity.

Journal of Virology
Junxian OuQiwei Zhang

Abstract

The current pandemic of COVID-19 is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 spike protein receptor-binding domain (RBD) is the critical determinant of viral tropism and infectivity. To investigate whether naturally occurring RBD mutations during the early transmission phase have altered the receptor binding affinity and infectivity, we first analyzed in silico the binding dynamics between SARS-CoV-2 RBD mutants and the human angiotensin-converting enzyme 2 (ACE2) receptor. Among 32,123 genomes of SARS-CoV-2 isolates (December 2019 through March 2020), 302 nonsynonymous RBD mutants were identified and clustered into 96 mutant types. The six dominant mutations were analyzed applying molecular dynamics simulations (MDS). The mutant type V367F continuously circulating worldwide displayed higher binding affinity to human ACE2 due to the enhanced structural stabilization of the RBD beta-sheet scaffold. The MDS also indicated that it would be difficult for bat SARS-like CoV to infect humans. However, the pangolin CoV is potentially infectious to humans. The increased infectivity of V367 mutants was further validated by performing receptor-ligand binding enzyme-linked ...Continue Reading

References

May 10, 2017·Nature Methods·Subha KalyaanamoorthyLars S Jermiin
Oct 3, 2017·Briefings in Bioinformatics·Kazutaka KatohKazunori D Yamada
Oct 14, 2017·Molecular Biology and Evolution·Julio RozasAlejandro Sánchez-Gracia
May 4, 2018·Molecular Biology and Evolution·Sudhir KumarKoichiro Tamura
May 23, 2018·Nucleic Acids Research·Andrew WaterhouseTorsten Schwede
May 24, 2018·Bioinformatics·James HadfieldRichard A Neher
Aug 29, 2019·Journal of Chemical Information and Modeling·Eko Aditya RifaiDaan P Geerke
Jan 25, 2020·The New England Journal of Medicine·Na ZhuUNKNOWN China Novel Coronavirus Investigating and Research Team
Jan 30, 2020·The New England Journal of Medicine·Qun LiZijian Feng
Feb 23, 2020·Science·Daniel WrappJason S McLellan
Feb 23, 2020·Biochemical and Biophysical Research Communications·Yun ChenZhizhuang Joe Zhao
Mar 11, 2020·Cell·Alexandra C WallsDavid Veesler
Mar 25, 2020·Emerging Microbes & Infections·Jianhui NieYouchun Wang
May 8, 2020·Nature·Kangpeng XiaoYongyi Shen
Jul 30, 2020·Viruses·Alessia LaiGianguglielmo Zehender
Oct 28, 2020·Nature·Jessica A PlantePei-Yong Shi
Mar 5, 2021·Science·Nicholas G DaviesW John Edmunds

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Citations

Aug 28, 2021·The Journal of Microbiology·Sandrine M SohHye-Ra Lee
Oct 26, 2021·Journal of King Saud University. Science·Palaniyandi VelusamyBaskaralingam Vaseeharan
Nov 18, 2021·Microbiology Spectrum·Mohammad AlkhatibFrancesca Ceccherini-Silberstein

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BETA
PCR
chip
ELISA
surface plasmon resonance
enzyme-linked immunosorbent assay

Software Mentioned

MAFFT
MODEL
Tree
DnaSP6
BioAider
BioEdit
IQ
Tree2
GROMACS
MFP ModelFinder

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