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Preprint (Author's original)Open Access (License Unspecified), Open
Preprint
VE607 Stabilizes SARS-CoV-2 Spike In the "RBD-up" Conformation and Inhibits Viral Entry
bioRxiv
22 Feb 2022
PMID: 35233570
Abstract
SARS-CoV-2 infection of host cells starts by binding of the Spike glycoprotein (S) to the ACE2 receptor. The S-ACE2 interaction is a potential target for therapies against COVID-19 as demonstrated by the development of immunotherapies blocking this interaction. Here, we present the commercially available VE607, comprised of three stereoisomers, that was originally described as an inhibitor of SARS-CoV-1. We show that VE607 specifically inhibits infection of SARS-CoV-1 and SARS-CoV-2 S-expressing pseudoviral particles as well as authentic SARS-CoV-2. VE607 stabilizes the receptor binding domain (RBD) in its 'up' conformation. In silico docking and mutational analysis map the VE607 binding site at the RBD-ACE2 interface. The IC50 values are in the low micromolar range for pseudoparticles derived from SARS-CoV-2 Wuhan/D614G as well as from variants of concern (Alpha, Beta, Gamma, Delta and Omicron), suggesting that VE607 has potential for the development of drugs against SARS-CoV-2 infections. Competing Interest Statement The authors have declared no competing interest.
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Details
- Title
- VE607 Stabilizes SARS-CoV-2 Spike In the "RBD-up" Conformation and Inhibits Viral Entry
- Creators
- Shilei Ding - Centre Hospitalier de l’Université de MontréalShang Yu Gong - McGill UniversityJonathan Grover - Yale UniversityMohammadjavad Mohammadi - Drexel University, Chemical and Biological EngineeringYaozong Chen - Uniformed Services University of the Health SciencesDani Vezina - Centre Hospitalier de l’Université de MontréalGuillaume Beaudoin-Bussieres - Centre Hospitalier de l’Université de MontréalVijay Tailor VermaGuillaume Goyette - Centre Hospitalier de l’Université de MontréalJonathan Richard - Centre Hospitalier de l’Université de MontréalDerek Yang - University of PennsylvaniaAmos Smith - University of PennsylvaniaMarzena Pazgier - Uniformed Services University of the Health SciencesMarceline Cote - University of OttawaCameron Abrams - Drexel University, Chemical and Biological EngineeringWalther Mothes - Yale UniversityAndres Finzi - Centre Hospitalier de l’Université de MontréalChristian Baron - Université de Montréal
- Publication Details
- bioRxiv
- Publisher
- Cold Spring Harbor Laboratory Press; Cold Spring Harbor
- Resource Type
- Preprint
- Language
- English
- Academic Unit
- Chemical and Biological Engineering
- Other Identifier
- 991021885915304721