ArticleThe Journal of infectious diseases2020
Impact of the Baloxavir-Resistant Polymerase Acid I38T Substitution on the Fitness of Contemporary Influenza A(H1N1)pdm09 and A(H3N2) Strains.
Article in The Journal of infectious diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed, 61 citations in OpenAlex.
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- Effectiveness of baloxavir marboxil in nonhuman primates infected with highly pathogenic avian influenza A(H7N9) virus.EBioMedicine · 2026Article
- From neuraminidase inhibitors to novel mechanisms: expanding therapeutic strategies against influenza.Frontiers in cellular and infection microbiology · 2026Review
- Thapsigargin suppresses porcine hemagglutinating encephalomyelitis virus replication by disrupting host energy metabolism.Virologica Sinica · 2025Article
- Identifying a Marine-Derived Small-Molecule Nucleoprotein Inhibitor Against Influenza A Virus.Marine drugs · 2025Article
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- Genotypic and phenotypic susceptibility of emerging avian influenza A viruses to neuraminidase and cap-dependent endonuclease inhibitors.Antiviral research · 2024Article
- A novel compound to overcome influenza drug resistance in endonuclease inhibitors.Molecular diversity · 2024Article
- The impact of PA/I38 substitutions and PA polymorphisms on the susceptibility of zoonotic influenza A viruses to baloxavir.Archives of virology · 2024Article
- Article
- Impact of Baloxavir Resistance-Associated Substitutions on Influenza Virus Growth and Drug Susceptibility.Journal of virology · 2023Article
- Viral Fitness of Baloxavir-Resistant Recombinant Influenza B/Victoria- and B/Yamagata-like Viruses Harboring the I38T PA Change, In Vitro, Ex Vivo and in Guinea Pigs.Microorganisms · 2023Article
- Observational
- Antiviral Approaches against Influenza Virus.Clinical microbiology reviews · 2023Review
- Carboxylic Acid Isostere Derivatives of Hydroxypyridinones as Core Scaffolds for Influenza Endonuclease Inhibitors.ACS medicinal chemistry letters · 2023Article
- Assessing the fitness of a dual-antiviral drug resistant human influenza virus in the ferret model.Communications biology · 2022Article
- Generation and Characterization of Drug-Resistant Influenza B Viruses Selected In Vitro with Baloxavir Acid.Pathogens (Basel, Switzerland) · 2022Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundBaloxavir is a cap-dependent inhibitor of the polymerase acid (PA) protein of influenza viruses. While appearing virologically superior to oseltamivir, baloxavir exhibits a low barrier of resistance. We sought to assess the impact of the common baloxavir-resistant I38T PA substitution on in vitro properties and virulence.
methodsInfluenza A/Quebec/144147/2009 (H1N1)pdm09 and A/Switzerland/9715293/2013 (H3N2) recombinant viruses and their I38T PA mutants were compared in single and competitive infection experiments in ST6GalI-MDCK cells and C57/BL6 mice. Virus titers in cell culture supernatants and lung homogenates were determined by virus yield assays. Ratios of wild-type (WT) and I38T mutant were assessed by digital RT-PCR.
resultsI38T substitution did not alter the replication kinetics of A(H1N1)pdm09 and A(H3N2) viruses. In competition experiments, a 50%:50% mixture evolved to 70%:30% (WT/mutant) for A(H1N1) and 88%:12% for A(H3N2) viruses after a single cell passage. The I38T substitution remained stable after 4 passages in vitro. In mice, the WT and its I38T mutant induced similar weight loss with comparable lung titers in both viral subtypes. The mutant virus tended to predominate over the WT in mouse competition experiments.
conclusionThe fitness of baloxavir-resistant I38T PA mutants appears relatively unaltered in seasonal subtypes warranting surveillance for its dissemination.
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