Identifying SARS-CoV-2 Entry Inhibitors through Drug Repurposing Screens of SARS-S and MERS-S Pseudotyped Particles

Catherine Z Chen; Miao Xu; Manisha Pradhan; Kirill Gorshkov; Jennifer D Petersen; Marco R Straus; Wei Zhu; Paul Shinn; Hui Guo; Min Shen; Carleen Klumpp-Thomas; Samuel G Michael; Joshua Zimmerberg; Wei Zheng; Gary R Whittaker

doi:10.1021/acsptsci.0c00112

Identifying SARS-CoV-2 Entry Inhibitors through Drug Repurposing Screens of SARS-S and MERS-S Pseudotyped Particles

ACS Pharmacol Transl Sci. 2020 Oct 19;3(6):1165-1175. doi: 10.1021/acsptsci.0c00112. eCollection 2020 Dec 11.

Authors

Affiliations

¹ National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
² Section on Integrative Biophysics, Division of Basic and Translational Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, United States.
³ Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, United States.

Abstract

While vaccine development will hopefully quell the global pandemic of COVID-19 caused by SARS-CoV-2, small molecule drugs that can effectively control SARS-CoV-2 infection are urgently needed. Here, inhibitors of spike (S) mediated cell entry were identified in a high throughput screen of an approved drugs library with SARS-S and MERS-S pseudotyped particle entry assays. We discovered six compounds (cepharanthine, abemaciclib, osimertinib, trimipramine, colforsin, and ingenol) to be broad spectrum inhibitors for spike-mediated entry. This work could contribute to the development of effective treatments against the initial stage of viral infection and provide mechanistic information that might aid the design of new drug combinations for clinical trials for COVID-19 patients.