Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease

Chunlong Ma, Brett Hurst, Yanmei Hu, Tommy Szeto, Bart Tarbet, View ORCID ProfileJun Wang
doi: https://doi.org/10.1101/2020.04.20.051581
Chunlong Ma
†Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, Arizona 85721, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brett Hurst
‡Institute for Antiviral Research, Utah State University, Logan, UT, USA
§Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yanmei Hu
†Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, Arizona 85721, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tommy Szeto
†Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, Arizona 85721, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bart Tarbet
‡Institute for Antiviral Research, Utah State University, Logan, UT, USA
§Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jun Wang
†Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, Arizona 85721, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jun Wang
  • For correspondence: junwang@pharmacy.arizona.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

A novel coronavirus SARS-CoV-2, also called novel coronavirus 2019 (nCoV-19), started to circulate among humans around December 2019, and it is now widespread as a global pandemic. The disease caused by SARS-CoV-2 virus is called COVID-19, which is highly contagious and has an overall mortality rate of 6.4% as of April 15, 2020. There is no vaccine or antiviral available for SARS-CoV-2. In this study, we report our discovery of inhibitors targeting the SARS-CoV-2 main protease (Mpro). Using the FRET-based enzymatic assay, several inhibitors including boceprevir, GC-376, calpain inhibitors II, XII, and MG-132 were identified to have potent activity with single-digit to submicromolar IC50 values in the enzymatic assay. The mechanism of action of the hits was further characterized using enzyme kinetic studies and thermal shift binding assays. Significantly, four compounds (boceprevir, GC-376, calpain inhibitors II and XII) inhibit SARS-CoV-2 viral replication in cell culture with EC50 values ranging from 0.49 to 3.37 μM. Notably, boceprevir, calpain inhibitors II and XII represent novel chemotypes that are distinct from known Mpro inhibitors. Overall, the compounds identified herein provide promising starting points for the further development of SARS-CoV-2 therapeutics.

Competing Interest Statement

J. W. and C. M. are inventors of a pending patent that claims the use of the identified compounds for COVID-19.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted April 20, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease
Chunlong Ma, Brett Hurst, Yanmei Hu, Tommy Szeto, Bart Tarbet, Jun Wang
bioRxiv 2020.04.20.051581; doi: https://doi.org/10.1101/2020.04.20.051581
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease
Chunlong Ma, Brett Hurst, Yanmei Hu, Tommy Szeto, Bart Tarbet, Jun Wang
bioRxiv 2020.04.20.051581; doi: https://doi.org/10.1101/2020.04.20.051581

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Pharmacology and Toxicology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4114)
  • Biochemistry (8816)
  • Bioengineering (6519)
  • Bioinformatics (23464)
  • Biophysics (11792)
  • Cancer Biology (9209)
  • Cell Biology (13325)
  • Clinical Trials (138)
  • Developmental Biology (7439)
  • Ecology (11412)
  • Epidemiology (2066)
  • Evolutionary Biology (15152)
  • Genetics (10439)
  • Genomics (14044)
  • Immunology (9172)
  • Microbiology (22159)
  • Molecular Biology (8813)
  • Neuroscience (47575)
  • Paleontology (350)
  • Pathology (1429)
  • Pharmacology and Toxicology (2492)
  • Physiology (3730)
  • Plant Biology (8082)
  • Scientific Communication and Education (1437)
  • Synthetic Biology (2221)
  • Systems Biology (6039)
  • Zoology (1253)