Structure of Furin Protease Binding to SARS-CoV‑2 Spike Glycoprotein and Implications for Potential Targets and Virulence

The COVID-19 pandemic is an urgent global health emergency, and the presence of Furin site in the SARS-CoV-2 spike glycoprotein alters virulence and warrants further molecular, structural, and biophysical studies. Here we report the structure of Furin in complex with SARS-CoV-2 spike glycoprotein, d...

Full description

Saved in:
Bibliographic Details
Published inThe Journal of Physical Chemistry Letters Vol. 11; no. 16; pp. 6655 - 6663
Main Author Vankadari, Naveen
Format Journal Article Web Resource
LanguageEnglish
Published United States American Chemical Society 20.08.2020
Subjects
Amino Acid Sequence
Animals
Betacoronavirus - chemistry
Betacoronavirus - pathogenicity
Catalytic Domain
CHO Cells
Cricetulus
Furin - chemistry
Furin - genetics
Furin - metabolism
Gene Expression - physiology
Hexosamines - metabolism
Humans
Letter
Molecular Docking Simulation
Molecular Dynamics Simulation
Physical Insights into Chemistry, Catalysis, and Interfaces
Protein Binding
Proteolysis
SARS-CoV-2
Serine Proteinase Inhibitors - metabolism
Spike Glycoprotein, Coronavirus - chemistry
Spike Glycoprotein, Coronavirus - metabolism
Virulence - physiology
Online AccessGet full text

Cover

More Information
Summary:The COVID-19 pandemic is an urgent global health emergency, and the presence of Furin site in the SARS-CoV-2 spike glycoprotein alters virulence and warrants further molecular, structural, and biophysical studies. Here we report the structure of Furin in complex with SARS-CoV-2 spike glycoprotein, demonstrating how Furin binds to the S1/S2 region of spike glycoprotein and eventually cleaves the viral protein using experimental functional studies, molecular dynamics, and docking. The structural studies underline the mechanism and mode of action of Furin, which is a key process in host cell entry and a hallmark of enhanced virulence. Our whole-exome sequencing analysis shows the genetic variants/alleles in Furin were found to alter the binding affinity for viral spike glycoprotein and could vary in infectivity in humans. Unravelling the mechanisms of Furin action, binding dynamics, and the genetic variants opens the growing arena of bona fide antibodies and development of potential therapeutics targeting the blockage of Furin cleavage.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1948-7185
1948-7185
DOI:10.1021/acs.jpclett.0c01698