ArticleNature communications2023
In vitro and in vivo characterization of SARS-CoV-2 resistance to ensitrelvir.
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 41 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.
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Who cites it
41 citing papers in PubMed, 75 citations in OpenAlex.
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- 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
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- Discovery of benzyl carbamate inhibitors of coronavirus MJournal of enzyme inhibition and medicinal chemistry · 2025Article
- SARS-CoV-2 Mpro inhibitor ensitrelvir: asymmetrical cross-resistance with nirmatrelvir and emerging resistance hotspots.Emerging microbes & infections · 2025Article
- A SARS-CoV-2 MNature communications · 2025Article
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- A luminescent attenuated SARS-CoV-2 for the identification and validation of drug-resistant mutants.Journal of virology · 2025Article
- The role of SARS-CoV-2 main protease in innate immune regulation: From molecular mechanisms to therapeutic implications.Acta pharmaceutica Sinica. B · 2025Review
- Evolution of Antiviral Drug Resistance in SARS-CoV-2.Viruses · 2025Review
- Application of novel dark-quencher labeled probes in multiplex qRT-PCR assays for rapid detection of SARS-CoV-2 variants.Journal of thoracic disease · 2025Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ensitrelvir, an oral antiviral agent that targets a SARS-CoV-2 main protease (3CLpro or Nsp5), is clinically useful against SARS-CoV-2 including its omicron variants. Since most omicron subvariants have reduced sensitivity to most monoclonal antibody therapies, SARS-CoV-2 resistance to other antivirals including main protease inhibitors such as ensitrelvir is a major public health concern. Here, repeating passages of SARS-CoV-2 in the presence of ensitrelvir revealed that the M49L and E166A substitutions in Nsp5 are responsible for reduced sensitivity to ensitrelvir. Both substitutions reduced in vitro virus growth in the absence of ensitrelvir. The combination of the M49L and E166A substitutions allowed the virus to largely evade the suppressive effect of ensitrelvir in vitro. The virus possessing Nsp5-M49L showed similar pathogenicity to wild-type virus, whereas the virus possessing Nsp5-E166A or Nsp5-M49L/E166A slightly attenuated. Ensitrelvir treatment of hamsters infected with the virus possessing Nsp5-M49L/E166A was ineffective; however, nirmatrelvir or molnupiravir treatment was effective. Therefore, it is important to closely monitor the emergence of ensitrelvir-resistant SARS-CoV-2 variants to guide antiviral treatment selection.
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Registered trials
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