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

The Journal of Physical Chemistry Letters
Naveen Vankadari


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.


Jun 10, 2003·Nature Structural Biology·Stefan HenrichManuel E Than
Sep 30, 2006·The Lancet Infectious Diseases·David BurgnerJenefer M Blackwell
Feb 13, 2010·Trends in Genetics : TIG·Ping An, Cheryl A Winkler
Mar 24, 2011·Heredity·P W Hedrick
Mar 29, 2014·ACS Chemical Biology·Sven O DahmsManuel E Than
Jan 8, 2015·Expert Opinion on Therapeutic Patents·Frédéric CoutureRobert Day
May 15, 2015·ChemMedChem·Kornelia HardesTorsten Steinmetzer
Oct 21, 2015·Biopreservation and Biobanking·Latarsha J Carithers, Helen M Moore
Aug 19, 2016·Nature·Monkol LekUNKNOWN Exome Aggregation Consortium
Sep 21, 2016·Proceedings of the National Academy of Sciences of the United States of America·Sven O DahmsManuel E Than
May 5, 2017·Nucleic Acids Research·Hongchun LiLee-Wei Yang
May 18, 2019·Proceedings of the National Academy of Sciences of the United States of America·Jessica C de GreefKevin P Campbell
Aug 14, 2019·Clinical & Translational Immunology·Elisabeth Braun, Daniel Sauter
Feb 18, 2020·The Lancet. Respiratory Medicine·Jinnong ZhangXuelin Chen
Feb 23, 2020·Science·Daniel WrappJason S McLellan
Mar 5, 2020·Nature Reviews. Drug Discovery·Guangdi Li, Erik De Clercq
Mar 11, 2020·Cell·Alexandra C WallsDavid Veesler
Apr 11, 2020·Journal of Biomolecular Structure & Dynamics·Anwarul HasanMojtaba Falahati
Apr 15, 2020·Nature Medicine·Kristian G AndersenRobert F Garry
Apr 17, 2020·Virus Evolution·John-Sebastian EdenUNKNOWN 2019-nCoV Study Group
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