Targeted protein degraders of SARS-CoV-2 Mpro are more active than enzymatic inhibition alone with activity against nirmatrelvir resistant virus
This work demonstrates the feasibility of generating degraders from viral protein inhibitors, and confirms that degraders possess higher antiviral potency and activity against resistant virus, compared to size matched non-degrading enzymatic inhibitors. These findings further support the development of targeted viral protein degraders as antiviral drugs, which may lead to more effective antiviral therapies for the future.
Authors
- Thomas Tran (ORCID: https://orcid.org/0000-0001-7931-0164)
- Simon J. Mountford (ORCID: https://orcid.org/0000-0002-0806-5197)
- Danielle Tilmanis
- Philip Evan Thompson (ORCID: https://orcid.org/0000-0002-5910-7625)
- Sam Greenall
- Seiya Yamayoshi (ORCID: https://orcid.org/0000-0001-7768-5157)
- Georgina Papadakis
- Kate E. Jarman (ORCID: https://orcid.org/0009-0000-5561-6636)
- Jake Shortt (ORCID: https://orcid.org/0000-0003-3185-6488)
- Nadia Warner (ORCID: https://orcid.org/0000-0002-4252-086X)
- Maki Kiso (ORCID: https://orcid.org/0009-0004-3645-0967)
- Belinda Maher (ORCID: https://orcid.org/0000-0002-8900-6876)
- Yoshihiro Kawaoka (ORCID: https://orcid.org/0000-0001-5061-8296)
- Danielle E. Anderson (ORCID: https://orcid.org/0000-0003-4791-5024)
- Baolong Pan (ORCID: https://orcid.org/0009-0003-4241-4519)
Institutions
- The Royal Melbourne Hospital (AU)
- University of Wisconsin–Madison (US)
- The University of Melbourne (AU)
- Walter and Eliza Hall Institute of Medical Research (AU)
- National Institute of Infectious Diseases (JP)
- Victorian Infectious Diseases Reference Laboratory (AU)
- National Center for Global Health and Medicine (JP)
- Peter Doherty Institute (AU)
- Monash Health (AU)
- Monash University (AU)
- Massachusetts Institute of Technology (US)
- The University of Tokyo (JP)
Publication Details
- Journal
- Communications Medicine
- Published
- 2025-04-26
- DOI
- https://doi.org/10.1038/s43856-025-00863-1
- Citations
- 12
- Primary Topic
- Protein Degradation and Inhibitors
- Type
- article
- Field-Weighted Citation Impact
- 9.67
Funders
- National Health and Medical Research Council