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ACS pharmacology & translational science
Dec 11, 2020;3 (6): 1165-1175.

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
Author Information
  1. Catherine Z Chen: National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
  2. Miao Xu: National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
  3. Manisha Pradhan: National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
  4. Kirill Gorshkov: National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
  5. Jennifer D Petersen: 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.
  6. Marco R Straus: Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, United States.
  7. Wei Zhu: National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
  8. Paul Shinn: National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
  9. Hui Guo: National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
  10. Min Shen: National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
  11. Carleen Klumpp-Thomas: National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
  12. Samuel G Michael: National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
  13. Joshua Zimmerberg: 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.
  14. Wei Zheng: National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
  15. Gary R Whittaker: Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, United States.
PMID: 33330839 DOI: 10.1021/acsptsci.0c00112

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.

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Journal Article
Article has an altmetric score of 63

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