VE607 stabilizes SARS-CoV-2 Spike in the “RBD-up” conformation and inhibits viral entry
Shilei Ding, Irfan Ullah, Shang Yu Gong, Jonathan R. Grover, Mohammadjavad Mohammadi, Yaozong Chen, Dani Vézina, Guillaume Beaudoin-Bussières, Vijay Tailor Verma, Guillaume Goyette, Fleur Gaudette, Jonathan Richard, Derek Yang, Amos B. Smith, Marzena Pazgier, Marceline Côté, Cameron F. Abrams, Priti Kumar, Walther Mothes, Pradeep D. Uchil, Andrés Finzi, Christian Baron
Abstract
docking, mutational analysis, and smFRET revealed that VE607 binds to the receptor binding domain (RBD)-ACE2 interface and stabilizes RBD in its "up" conformation. Prophylactic treatment with VE607 did not prevent SARS-CoV-2-induced mortality in K18-hACE2 mice, but it did reduce viral replication in the lungs by 37-fold. Thus, VE607 is an interesting lead for drug development for the treatment of SARS-CoV-2 infection.