RT Journal Article
SR Electronic
T1 VE607 Stabilizes SARS-CoV-2 Spike In the “RBD-up” Conformation and Inhibits Viral Entry
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.02.03.479007
DO 10.1101/2022.02.03.479007
A1 Shilei Ding
A1 Shang Yu Gong
A1 Jonathan Grover
A1 Mohammadjavad Mohammadi
A1 Yaozong Chen
A1 Dani Vézina
A1 Guillaume Beaudoin-Bussières
A1 Vijay Tailor Verma
A1 Guillaume Goyette
A1 Jonathan Richard
A1 Derek Yang
A1 Amos B. Smith III
A1 Marzena Pazgier
A1 Marceline Côté
A1 Cameron Abrams
A1 Walther Mothes
A1 Andrés Finzi
A1 Christian Baron
YR 2022
UL http://biorxiv.org/content/early/2022/02/04/2022.02.03.479007.abstract
AB 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 StatementThe authors have declared no competing interest.