ArticleInfluenza and other respiratory viruses2021
Comprehensive assessment of amino acid substitutions in the trimeric RNA polymerase complex of influenza A virus detected in clinical trials of baloxavir marboxil.
Article in Influenza and other respiratory viruses, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Influenza A(H1N1)pdm09 Virus with Reduced Susceptibility to Baloxavir, Japan, 2024.Emerging infectious diseases · 2025Article
- High-resolution melting analysis for detection of nucleotide mutation markers in the polymerase-acidic (PA) gene of influenza virus that are associated with baloxavir marboxil resistance.Archives of virology · 2025Article
- The impact of PA/I38 substitutions and PA polymorphisms on the susceptibility of zoonotic influenza A viruses to baloxavir.Archives of virology · 2024Article
- Study on the clinical efficacy and safety of baloxavir marboxil tablets in the treatment of influenza A.Frontiers in medicine · 2024Article
- Prophylactic Treatment with Baloxavir Protects Mice from Lethal Infection with Influenza A and B Viruses.Viruses · 2023Article
- Impact of Baloxavir Resistance-Associated Substitutions on Influenza Virus Growth and Drug Susceptibility.Journal of virology · 2023Article
- In Vivo Antiviral Activity of Baloxavir against PA/I38T-Substituted Influenza A Viruses at Clinically Relevant Doses.Viruses · 2023Article
- Antiviral Approaches against Influenza Virus.Clinical microbiology reviews · 2023Review
- Article
- Influenza A virus polymerase acidic protein E23G/K substitutions weaken key baloxavir drug-binding contacts with minimal impact on replication and transmission.PLoS pathogens · 2022Article
- Influenza antivirals and animal models.FEBS open bio · 2022Review
- Pleiotropic Effects of Influenza H1, H3, and B Baloxavir-Resistant Substitutions on Replication, Sensitivity to Baloxavir, and Interferon Expression.Antimicrobial agents and chemotherapy · 2022Article
- Global update on the susceptibilities of human influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2018-2020.Antiviral research · 2022Review
- Exploration of the 2,3-dihydroisoindole pharmacophore for inhibition of the influenza virus PA endonuclease.Bioorganic chemistry · 2021Article
- Influenza polymerase inhibitor resistance: Assessment of the current state of the art - A report of the isirv Antiviral group.Antiviral research · 2021Review
- Whole-Genome Analysis Surveillance of Influenza A Virus Resistance to Polymerase Complex Inhibitors in Eastern Spain from 2016 to 2019.Antimicrobial agents and chemotherapy · 2021Article
- Comprehensive assessment of amino acid substitutions in the trimeric RNA polymerase complex of influenza A virus detected in clinical trials of baloxavir marboxil.Influenza and other respiratory viruses · 2021Article
- Multiple polymerase acidic (PA) I38X substitutions in influenza A(H1N1)pdm09 virus permit polymerase activity and cause reduced baloxavir inhibition.The Journal of antimicrobial chemotherapy · 2021Article
- Development and Effects of Influenza Antiviral Drugs.Molecules (Basel, Switzerland) · 2021Review
- Anno 2021: Which antivirals for the coming decade?Annual reports in medicinal chemistry · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBaloxavir marboxil (BXM) is an approved drug that selectively targets cap-dependent endonuclease on PA subunit in the RNA polymerase complex of influenza A and B viruses. Amino acid substitutions at position 38 in the PA subunit were identified as a major pathway for reduced susceptibility to baloxavir acid (BXA), the active form of BXM. Additionally, substitutions found at positions E23, A37, and E199 in the PA subunit impact BXA susceptibility by less than 10-fold.
methodsWe comprehensively evaluated the impact of novel amino acid substitutions identified in PA, PB1, and PB2 subunits in BXM clinical trials and influenza sequence databases by means of drug susceptibility and replicative capacity.
resultsPA/I38N in A(H1N1)pdm09 and PA/I38R in A(H3N2) were newly identified as treatment-emergent substitutions in the CAPSTONE-2 study. The I38N substitution conferred reduced susceptibility by 24-fold, whereas replicative capacity of the I38N-substituted virus was impaired compared with the wild-type. The I38R-substituted virus was not viable in cell culture. All other mutations assessed in this extensive study did not significantly affect BXA susceptibility (< 2.4-fold change).
conclusionThese results provide additional information on the impact of amino acid substitutions in the trimeric viral polymerase complex to BXA susceptibility and will further support influenza surveillance.
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