A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike

Science Advances
Shuai XiaLu Lu


Continuously emerging highly pathogenic human coronaviruses (HCoVs) remain a major threat to human health, as illustrated in past SARS-CoV and MERS-CoV outbreaks. The development of a drug with broad-spectrum HCoV inhibitory activity would address this urgent unmet medical need. Although previous studies have suggested that the HR1 of HCoV spike (S) protein is an important target site for inhibition against specific HCoVs, whether this conserved region could serve as a target for the development of broad-spectrum pan-CoV inhibitor remains controversial. Here, we found that peptide OC43-HR2P, derived from the HR2 domain of HCoV-OC43, exhibited broad fusion inhibitory activity against multiple HCoVs. EK1, the optimized form of OC43-HR2P, showed substantially improved pan-CoV fusion inhibitory activity and pharmaceutical properties. Crystal structures indicated that EK1 can form a stable six-helix bundle structure with both short α-HCoV and long β-HCoV HR1s, further supporting the role of HR1 region as a viable pan-CoV target site.


Dec 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·S Marqusee, R L Baldwin
Oct 11, 1994·Proceedings of the National Academy of Sciences of the United States of America·C T WildT J Matthews
Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Jan 24, 1998·Journal of Biomolecular Structure & Dynamics·M Lu, P S Kim
Oct 12, 2000·Journal of Virology·S WatanabeY Kawaoka
Oct 2, 2002·Nature Biotechnology·Marielle CavroisWarner C Greene
Nov 1, 2003·Virology·Hélène Jacomy, Pierre J Talbot
May 20, 2004·Proceedings of the National Academy of Sciences of the United States of America·Berend Jan BoschPeter J M Rottier
Jun 25, 2004·Nucleic Acids Research·Todd J DolinskyNathan A Baker
Sep 24, 2004·Virology·Marielle CavroisWarner C Greene
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
May 24, 2005·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Susan S ChiuJ S M Peiris
Mar 14, 2007·Pediatric Pulmonology·Arne SimonOliver Schildgen
Feb 26, 2009·The Journal of Infectious Diseases·Geoffrey J GorseKristin L Nichol
Jul 8, 2009·Trends in Molecular Medicine·So-Young ChoiStefan Pöhlmann
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Jan 23, 2013·The Pediatric Infectious Disease Journal·Andréanne JeanMakeda Semret
May 2, 2014·Nucleic Acids Research·Marco BiasiniTorsten Schwede

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Methods Mentioned

circular dichroism
enzyme-linked immunosorbent assay
flow cytometry

Software Mentioned

GraphPad Prism
PyMOL Molecular Graphics System
Schrödinger Suite
Swiss Model

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