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

Main protease mutants of SARS-CoV-2 variants remain susceptible to PF-07321332

View ORCID ProfileSven Ullrich, View ORCID ProfileKasuni B. Ekanayake, View ORCID ProfileGottfried Otting, View ORCID ProfileChristoph Nitsche
doi: https://doi.org/10.1101/2021.11.28.470226
Sven Ullrich
Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sven Ullrich
Kasuni B. Ekanayake
Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Kasuni B. Ekanayake
Gottfried Otting
Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Gottfried Otting
Christoph Nitsche
Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Christoph Nitsche
  • For correspondence: christoph.nitsche@anu.edu.au
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

The COVID-19 pandemic continues to be a public health threat. Multiple mutations in the spike protein of emerging variants of SARS-CoV-2 appear to impact on the effectiveness of available vaccines. Specific antiviral agents are keenly anticipated but their efficacy may also be compromised in emerging variants. One of the most attractive coronaviral drug targets is the main protease (Mpro). A promising Mpro inhibitor of clinical relevance is the peptidomimetic PF-07321332. We expressed Mpro of five SARS-CoV-2 lineages (C.37 Lambda, B.1.1.318, B.1.2, B.1.351 Beta, P.2 Zeta), each of which carries a strongly prevalent missense mutation (G15S, T21I, L89F, K90R, L205V). Enzyme kinetics showed that these Mpro variants are similarly catalytically competent as the wildtype. We show that PF-07321332 has similar potency against the variants as against the wildtype. Our in vitro data suggest that the efficacy of specific Mpro inhibitors such as PF-07321332 is not compromised in current COVID-19 variants.

Figure
  • Download figure
  • Open in new tab

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. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted November 30, 2021.
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.
Main protease mutants of SARS-CoV-2 variants remain susceptible to PF-07321332
(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
Main protease mutants of SARS-CoV-2 variants remain susceptible to PF-07321332
Sven Ullrich, Kasuni B. Ekanayake, Gottfried Otting, Christoph Nitsche
bioRxiv 2021.11.28.470226; doi: https://doi.org/10.1101/2021.11.28.470226
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Main protease mutants of SARS-CoV-2 variants remain susceptible to PF-07321332
Sven Ullrich, Kasuni B. Ekanayake, Gottfried Otting, Christoph Nitsche
bioRxiv 2021.11.28.470226; doi: https://doi.org/10.1101/2021.11.28.470226

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

  • Biochemistry
Subject Areas
All Articles
  • Animal Behavior and Cognition (3513)
  • Biochemistry (7358)
  • Bioengineering (5337)
  • Bioinformatics (20303)
  • Biophysics (10033)
  • Cancer Biology (7761)
  • Cell Biology (11329)
  • Clinical Trials (138)
  • Developmental Biology (6443)
  • Ecology (9968)
  • Epidemiology (2065)
  • Evolutionary Biology (13344)
  • Genetics (9364)
  • Genomics (12597)
  • Immunology (7718)
  • Microbiology (19057)
  • Molecular Biology (7452)
  • Neuroscience (41100)
  • Paleontology (300)
  • Pathology (1233)
  • Pharmacology and Toxicology (2141)
  • Physiology (3171)
  • Plant Biology (6867)
  • Scientific Communication and Education (1275)
  • Synthetic Biology (1899)
  • Systems Biology (5320)
  • Zoology (1090)