ArticleNature communications2023
In vitro and in vivo characterization of SARS-CoV-2 strains resistant to nirmatrelvir.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 40 citations in OpenAlex.
- Host-directed antiviral strategy targeting prohibitins: Mel56 suppresses influenza A virus and severe acute respiratory syndrome coronavirus 2 via modulation of antioxidant pathways and mitochondrial function.Microbiology spectrum · 2026Article
- SARS-CoV-2 3CLpro mutations T21I and E166A confer differential resistance to simnotrelvir, bofutrelvir, and ensitrelvir.Journal of virology · 2026Article
- Cross-resistance patterns in SARS-CoV-2 against 3CL protease inhibitors.Nature communications · 2026Article
- Next-generation inhibitors of SARS-CoV-2 MNature communications · 2026Article
- Structure-Based Development of Ultra-Broad-Spectrum 3C-Like Protease Inhibitors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Structure-Based Design of Covalent SARS-CoV‑2 Main Protease Inhibitors Targeting the Nirmatrelvir-Resistant E166 Mutants.JACS Au · 2026Article
- The Redesign of the Molecular Scaffold of Viral Ion Channel Blockers.Computational and structural biotechnology journal · 2026Article
- Structural insights into the nirmatrelvir-resistant SARS-CoV-2 MRSC medicinal chemistry · 2025Article
- D2Screen: Embedding Pretrained Representation Learning Model and Molecular Docking for Virtual Screening.ACS medicinal chemistry letters · 2025Article
- SARS-CoV‑2 Main Protease Inhibitors Containing 5‑Substituted Benzothiazole-2-carbonyl Moieties at the P1' Site and Their Derivatives.ACS omega · 2025Article
- An orally available MNature communications · 2025Article
- Identification of naturally occurring drug-resistant mutations of SARS-CoV-2 papain-like protease.Nature communications · 2025Article
- Development of viral infectious clones and their applications based on yeast and bacterial artificial chromosome platforms.Molecular biomedicine · 2025Review
- Targeted protein degraders of SARS-CoV-2 Mpro are more active than enzymatic inhibition alone with activity against nirmatrelvir resistant virus.Communications medicine · 2025Article
- Design of quinoline SARS-CoV-2 papain-like protease inhibitors as oral antiviral drug candidates.Nature communications · 2025Article
- Distal protein-protein interactions contribute to nirmatrelvir resistance.Nature communications · 2025Article
- An Investigation of Nirmatrelvir (Paxlovid) Resistance in SARS-CoV-2 MACS bio & med chem Au · 2024Article
- Newly Proposed Dose of Daclatasvir to Prevent Lethal SARS-CoV-2 Infection in Human Transgenic ACE-2 Mice.Viruses · 2024Article
- Structure-Based Design of Covalent SARS-CoV-2 Papain-like Protease Inhibitors.Journal of medicinal chemistry · 2024Article
- An oral non-covalent non-peptidic inhibitor of SARS-CoV-2 Mpro ameliorates viral replication and pathogenesis in vivo.Cell reports · 2024Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nirmatrelvir, an oral antiviral agent that targets a SARS-CoV-2 main protease (3CLpro), is clinically useful against infection with SARS-CoV-2 including its omicron variants. Since most omicron subvariants have reduced sensitivity to many monoclonal antibody therapies, potential SARS-CoV-2 resistance to nirmatrelvir is a major public health concern. Several amino acid substitutions have been identified as being responsible for reduced susceptibility to nirmatrelvir. Among them, we selected L50F/E166V and L50F/E166A/L167F in the 3CLpro because these combinations of substitutions are unlikely to affect virus fitness. We prepared and characterized delta variants possessing Nsp5-L50F/E166V and Nsp5-L50F/E166A/L167F. Both mutant viruses showed decreased susceptibility to nirmatrelvir and their growth in VeroE6/TMPRSS2 cells was delayed. Both mutant viruses showed attenuated phenotypes in a male hamster infection model, maintained airborne transmissibility, and were outcompeted by wild-type virus in co-infection experiments in the absence of nirmatrelvir, but less so in the presence of the drug. These results suggest that viruses possessing Nsp5-L50F/E166V and Nsp5-L50F/E166A/L167F do not become dominant in nature. However, it is important to closely monitor the emergence of nirmatrelvir-resistant SARS-CoV-2 variants because resistant viruses with additional compensatory mutations could emerge, outcompete the wild-type virus, and become dominant.
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