Functional and Structural Characterization of Treatment-Emergent Nirmatrelvir Resistance Mutations at Low Frequencies in the Main Protease (Mpro) Reveals a Unique Evolutionary Route for SARS-CoV-2 to Gain Resistance
Our new Mpro clinical mutations that confer complete resistance to NIR were not identified during previous cell-culture-based studies. More research is needed to explore resistance mechanisms, providing insights into strategies that mitigate resistance and protect therapeutic efficacy.
Authors
- Natalie M. Deschenes (ORCID: https://orcid.org/0000-0003-2306-2661)
- Calem Kenward (ORCID: https://orcid.org/0000-0002-3771-0044)
- Abdullah Moinuddin
- Allison McGeer (ORCID: https://orcid.org/0000-0001-5647-6137)
- Merrilee Thomas (ORCID: https://orcid.org/0000-0002-3430-0912)
- Patryk Aftanas (ORCID: https://orcid.org/0000-0003-0437-5929)
- N.C.J. Strynadka (ORCID: https://orcid.org/0000-0002-4058-9425)
- L.J. Worrall (ORCID: https://orcid.org/0000-0003-4966-7175)
- Robert Andrew Kozak (ORCID: https://orcid.org/0000-0002-6159-9972)
- Lubna Farooqi
- Mark Paetzel (ORCID: https://orcid.org/0000-0002-7408-5487)
- Aoxiang Li
- Finlay Maguire (ORCID: https://orcid.org/0000-0002-1203-9514)
- François Jean (ORCID: https://orcid.org/0000-0002-6148-7460)
- W.A. Mosimann
- Iqbal Malik (ORCID: https://orcid.org/0000-0002-0883-5614)
- Jason R. Smith (ORCID: https://orcid.org/0000-0001-7380-2192)
- Robert N. Young (ORCID: https://orcid.org/0000-0002-8235-6080)
- Artem Cherkasov (ORCID: https://orcid.org/0000-0002-1599-1439)
- Jimena Pérez‐Vargas (ORCID: https://orcid.org/0000-0002-4337-7903)
- Maxime Lefebvre
- Zoë Zhong
- Jeonghwan Lim
- Nicholas Waglechner (ORCID: https://orcid.org/0000-0003-1758-1158)
- Lina Siddiqi
Institutions
- Mount Sinai Hospital (CA)
- Dalhousie University (CA)
- Sunnybrook Health Science Centre (CA)
- University of British Columbia (CA)
- Simon Fraser University (CA)
- University of Toronto (CA)
- Montana Molecular (United States) (US)
- Prevention of Organ Failure (CA)
- Sinai Health System (CA)
- The Prostate Centre (GB)
- Sunnybrook Hospital (CA)
- Sunnybrook Research Institute
Publication Details
- Journal
- The Journal of Infectious Diseases
- Published
- 2025-06-02
- DOI
- https://doi.org/10.1093/infdis/jiaf294
- Citations
- 1
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 1.40
Funders
- University of Saskatchewan
- National Research Council Sri Lanka
- Canada Foundation for Innovation
- National Institutes of Health
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- National Institute of Allergy and Infectious Diseases