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

Calpain-2 mediates SARS-CoV-2 entry and represents a therapeutic target

Qiru Zeng, Avan Antia, Maritza Puray-Chavez, Sebla B. Kutluay, Siyuan Ding
doi: https://doi.org/10.1101/2022.11.29.518418
Qiru Zeng
1Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Avan Antia
1Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maritza Puray-Chavez
1Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sebla B. Kutluay
1Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Siyuan Ding
1Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: siyuan.ding@wustl.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

ABSTRACT

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, much effort has been dedicated to identifying effective antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A number of calpain inhibitors show excellent antiviral activities against SARS-CoV-2 by targeting the viral main protease (Mpro), which plays an essential role in processing viral polyproteins. In this study, we found that calpain inhibitors potently inhibited the infection of a chimeric vesicular stomatitis virus (VSV) encoding the SARS-CoV-2 spike protein, but not Mpro. In contrast, calpain inhibitors did not exhibit antiviral activities towards the wild-type VSV with its native glycoprotein. Genetic knockout of calpain-2 by CRISPR/Cas9 conferred resistance of the host cells to the chimeric VSV-SARS-CoV-2 virus and a clinical isolate of wild-type SARS-CoV-2. Mechanistically, calpain-2 facilitates SARS-CoV-2 spike protein-mediated cell attachment by positively regulating the cell surface levels of ACE2. These results highlight an Mpro-independent pathway targeted by calpain inhibitors for efficient viral inhibition. We also identify calpain-2 as a novel host factor and a potential therapeutic target responsible for SARS-CoV-2 infection at the entry step.

Competing Interest Statement

The authors have declared no competing interest.

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.
Back to top
PreviousNext
Posted November 29, 2022.
Download PDF

Supplementary Material

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.
Calpain-2 mediates SARS-CoV-2 entry and represents a therapeutic target
(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
Calpain-2 mediates SARS-CoV-2 entry and represents a therapeutic target
Qiru Zeng, Avan Antia, Maritza Puray-Chavez, Sebla B. Kutluay, Siyuan Ding
bioRxiv 2022.11.29.518418; doi: https://doi.org/10.1101/2022.11.29.518418
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Calpain-2 mediates SARS-CoV-2 entry and represents a therapeutic target
Qiru Zeng, Avan Antia, Maritza Puray-Chavez, Sebla B. Kutluay, Siyuan Ding
bioRxiv 2022.11.29.518418; doi: https://doi.org/10.1101/2022.11.29.518418

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

  • Microbiology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4229)
  • Biochemistry (9109)
  • Bioengineering (6753)
  • Bioinformatics (23944)
  • Biophysics (12103)
  • Cancer Biology (9498)
  • Cell Biology (13745)
  • Clinical Trials (138)
  • Developmental Biology (7617)
  • Ecology (11664)
  • Epidemiology (2066)
  • Evolutionary Biology (15479)
  • Genetics (10620)
  • Genomics (14297)
  • Immunology (9467)
  • Microbiology (22800)
  • Molecular Biology (9078)
  • Neuroscience (48894)
  • Paleontology (355)
  • Pathology (1479)
  • Pharmacology and Toxicology (2566)
  • Physiology (3824)
  • Plant Biology (8309)
  • Scientific Communication and Education (1467)
  • Synthetic Biology (2291)
  • Systems Biology (6172)
  • Zoology (1297)