ArticlePLoS pathogens2024
A comprehensive study of SARS-CoV-2 main protease (Mpro) inhibitor-resistant mutants selected in a VSV-based system.
Article in PLoS pathogens, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Orally Bioavailable SARS-CoV-2 Protease Inhibitors Bearing a Hydroxymethyl Ketone Warhead.Viruses · 2026Article
- Characterization of the Cross-Resistance of SARS-CoV‑2 Main Protease Inhibitors, Ibuzatrelvir, Ensitrelvir, and Nirmatrelvir.ACS pharmacology & translational science · 2026Article
- Structural Basis and Inhibitor Development of SARS-CoV-2 Papain-like Protease.Molecules (Basel, Switzerland) · 2026Review
- Discerning dangerous gain of function: most gain of function (GoF) research does not involve infectious microbes.Frontiers in bioengineering and biotechnology · 2026Review
- A public health perspective of SARS-CoV-2 evolution and surveillance strategies in Germany from 2020 to 2023.Communications medicine · 2025Review
- P2YACS pharmacology & translational science · 2025Article
- Photosensitizer-conjugated lignin nanoparticles for photodynamic antimicrobial inactivation.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2025Article
- Thermal Titration Molecular Dynamics: The Revenge of the Fragments.Journal of chemical information and modeling · 2025Article
- Phytoconstituents of Citrus limon (Lemon) as Potential Inhibitors Against Multi Targets of SARS-CoV-2 by Use of Molecular Modelling and In Vitro Determination Approaches.ChemistryOpen · 2024Article
- Emerging SARS-CoV-2 Resistance After Antiviral Treatment.JAMA network open · 2024Article
- Why Certain Repurposed Drugs Are Unlikely to Be Effective Antivirals to Treat SARS-CoV-2 Infections.Viruses · 2024Article
- An orally bioavailable SARS-CoV-2 main protease inhibitor exhibits improved affinity and reduced sensitivity to mutations.Science translational medicine · 2024Article
- Study of key residues in MERS-CoV and SARS-CoV-2 main proteases for resistance against clinically applied inhibitors nirmatrelvir and ensitrelvir.Npj viruses · 2024Article
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29 authors.
Funding
Abstract
Nirmatrelvir was the first protease inhibitor specifically developed against the SARS-CoV-2 main protease (3CLpro/Mpro) and licensed for clinical use. As SARS-CoV-2 continues to spread, variants resistant to nirmatrelvir and other currently available treatments are likely to arise. This study aimed to identify and characterize mutations that confer resistance to nirmatrelvir. To safely generate Mpro resistance mutations, we passaged a previously developed, chimeric vesicular stomatitis virus (VSV-Mpro) with increasing, yet suboptimal concentrations of nirmatrelvir. Using Wuhan-1 and Omicron Mpro variants, we selected a large set of mutants. Some mutations are frequently present in GISAID, suggesting their relevance in SARS-CoV-2. The resistance phenotype of a subset of mutations was characterized against clinically available protease inhibitors (nirmatrelvir and ensitrelvir) with cell-based, biochemical and SARS-CoV-2 replicon assays. Moreover, we showed the putative molecular mechanism of resistance based on in silico molecular modelling. These findings have implications on the development of future generation Mpro inhibitors, will help to understand SARS-CoV-2 protease inhibitor resistance mechanisms and show the relevance of specific mutations, thereby informing treatment decisions.
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