ArticlemBio2025
Molecular mechanisms of drug resistance and compensation in SARS-CoV-2 main protease: the interplay between E166 and L50.
Article in mBio, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
4 citing papers in PubMed.
- Effect of inhaled interferon-β1a on SARS-CoV-2 diversity and evolution.Microbiology spectrum · 2026Trial
- Nitrile-Based Inhibitors Targeting both SARS-CoV‑2 Main Protease and Human Cathepsin L.ACS medicinal chemistry letters · 2026Article
- Cooperativity and communication between the active sites of the dimeric SARS-CoV-2 main protease.Science advances · 2026Article
- Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
The SARS-CoV-2 main protease (M IMPORTANCE: Drug resistance remains a great challenge to modern medicine. This study investigates SARS-CoV-2 main protease variants E166A and E166V which confer nirmatrelvir resistance. These variants can retain considerable enzymatic activity through combination with the compensatory mutation L50F. For single- and double-mutant variant enzymes, we assessed catalytic efficiency, measured loss in potency for nirmatrelvir and its analog PF-00835231, and cocrystallized with inhibitors to investigate drug resistance caused by these mutations. Our results contribute toward understanding of molecular mechanisms of resistance and combinations of mutations, which pushes toward resistance-thwarting inhibitor design. These principles also apply broadly to many quickly evolving drug targets in infectious diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.