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A repurposed drug screen identifies compounds that inhibit the binding of the COVID-19 spike protein to ACE2

Kaleb B. Tsegay, Christiana M. Adeyemi, Edward P. Gniffke, D. Noah Sather, John K. Walker, View ORCID ProfileStephen E. P. Smith
doi: https://doi.org/10.1101/2021.04.08.439071
Kaleb B. Tsegay
1Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 98101
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Christiana M. Adeyemi
2St. Louis University School of Medicine, Department of Pharmacology and Physiology, St. Louis, MO 63110
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Edward P. Gniffke
1Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 98101
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D. Noah Sather
3Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, WA, 98101
4University of Washington, Department of Pediatrics, Seattle, WA 98195
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John K. Walker
2St. Louis University School of Medicine, Department of Pharmacology and Physiology, St. Louis, MO 63110
5Henry and Amelia Nasrallah Center for Neuroscience, Saint Louis University St. Louis, MO 63110
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Stephen E. P. Smith
1Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 98101
4University of Washington, Department of Pediatrics, Seattle, WA 98195
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  • ORCID record for Stephen E. P. Smith
  • For correspondence: seps@uw.edu
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Abstract

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 Statement

SCRI has submitted a provisional patent on the assay and compounds described in this manuscript.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 08, 2021.
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A repurposed drug screen identifies compounds that inhibit the binding of the COVID-19 spike protein to ACE2
Kaleb B. Tsegay, Christiana M. Adeyemi, Edward P. Gniffke, D. Noah Sather, John K. Walker, Stephen E. P. Smith
bioRxiv 2021.04.08.439071; doi: https://doi.org/10.1101/2021.04.08.439071
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A repurposed drug screen identifies compounds that inhibit the binding of the COVID-19 spike protein to ACE2
Kaleb B. Tsegay, Christiana M. Adeyemi, Edward P. Gniffke, D. Noah Sather, John K. Walker, Stephen E. P. Smith
bioRxiv 2021.04.08.439071; doi: https://doi.org/10.1101/2021.04.08.439071

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