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[Preprint]. 2022 Feb 22:2022.02.03.479007.
doi: 10.1101/2022.02.03.479007.

VE607 Stabilizes SARS-CoV-2 Spike In the "RBD-up" Conformation and Inhibits Viral Entry

Shilei Ding, Shang Yu Gong, Jonathan Grover, Mohammadjavad Mohammadi, Yaozong Chen, Dani Vézina, Guillaume Beaudoin-Bussières, Vijay Tailor Verma, Guillaume Goyette, Jonathan Richard, Derek Yang, Amos B Smith, Marzena Pazgier, Marceline Côté, Cameron Abrams, Walther Mothes, Andrés Finzi, Christian Baron

VE607 Stabilizes SARS-CoV-2 Spike In the "RBD-up" Conformation and Inhibits Viral Entry

Shilei Ding et al. bioRxiv. .

Update in

  • VE607 stabilizes SARS-CoV-2 Spike in the "RBD-up" conformation and inhibits viral entry.
    Ding S, Ullah I, Gong SY, Grover JR, Mohammadi M, Chen Y, Vézina D, Beaudoin-Bussières G, Verma VT, Goyette G, Gaudette F, Richard J, Yang D, Smith AB 3rd, Pazgier M, Côté M, Abrams C, Kumar P, Mothes W, Uchil PD, Finzi A, Baron C. Ding S, et al. iScience. 2022 Jul 15;25(7):104528. doi: 10.1016/j.isci.2022.104528. Epub 2022 Jun 3. iScience. 2022. PMID: 35677392 Free PMC article.

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 IC 50 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.

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