RT Journal Article
SR Electronic
T1 A repurposed drug screen identifies compounds that inhibit the binding of the COVID-19 spike protein to ACE2
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.04.08.439071
DO 10.1101/2021.04.08.439071
A1 Kaleb B. Tsegay
A1 Christiana M. Adeyemi
A1 Edward P. Gniffke
A1 D. Noah Sather
A1 John K. Walker
A1 Stephen E. P. Smith
YR 2021
UL http://biorxiv.org/content/early/2021/04/08/2021.04.08.439071.abstract
AB Repurposed drugs that block the interaction between the SARS-CoV-2 spike protein and its receptor ACE2 could offer a rapid route to novel COVID-19 treatments or prophylactics. Here, we screened 2701 compounds from a commercial library of drugs approved by international regulatory agencies for their ability to inhibit the binding of recombinant, trimeric SARS-CoV-2 spike protein to recombinant human ACE2. We identified 56 compounds that inhibited binding by <90%, measured the EC50 of binding inhibition, and computationally modeled the docking of the best inhibitors to both Spike and ACE2. These results highlight an effective screening approach to identify compounds capable of disrupting the Spike-ACE2 interaction as well as identifying several potential inhibitors that could serve as templates for future drug discovery efforts.Competing Interest StatementSCRI has submitted a provisional patent on the assay and compounds described in this manuscript.