ArticleAntimicrobial agents and chemotherapy2014
Characterization of drug-resistant influenza virus A(H1N1) and A(H3N2) variants selected in vitro with laninamivir.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 53 citations in OpenAlex.
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- Progress of Influenza Viruses and Inhibitors.Current medicinal chemistry · 2025Review
- The Development History, Structural Composition, and Functions of Influenza Viruses and the Progress of Influenza Virus Inhibitors in Clinics and Clinical Trials.Mini reviews in medicinal chemistry · 2025Review
- Influenza neuraminidase mutations and resistance to neuraminidase inhibitors.Emerging microbes & infections · 2024Review
- The Synergistic Effect of Baloxavir and Neuraminidase Inhibitors against Influenza Viruses In Vitro.Viruses · 2024Article
- Recent Advances, Approaches and Challenges in the Development of Universal Influenza Vaccines.Influenza and other respiratory viruses · 2024Review
- High pathogenic avian influenza A(H5) viruses of clade 2.3.4.4b in Europe-Why trends of virus evolution are more difficult to predict.Virus evolution · 2024Article
- Role of ROCK signaling in virus replication.Virus research · 2023Review
- Influenza Treatment: Limitations of Antiviral Therapy and Advantages of Drug Combination Therapy.Microorganisms · 2023Review
- Recent advances in potential drug therapies combating COVID-19 and related coronaviruses-A perspective.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2021Review
- Bat-Borne Influenza A Viruses: An Awakening.Cold Spring Harbor perspectives in medicine · 2021Review
- Integrating evolutionary aspects into dual-use discussion: the cases of influenza virus and enterohemorrhagicEvolution, medicine, and public health · 2021Review
- Laninamivir-Interferon Lambda 1 Combination Treatment Promotes Resistance by Influenza A Virus More Rapidly than Laninamivir Alone.Antimicrobial agents and chemotherapy · 2020Article
- Next-generation influenza vaccines: opportunities and challenges.Nature reviews. Drug discovery · 2020Review
- Reduced Susceptibility to Neuraminidase Inhibitors in Influenza B Isolate, Canada.Emerging infectious diseases · 2019Article
- Article
- Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors and status of novel antivirals, 2016-2017.Antiviral research · 2018Article
- Combination Therapy With Neuraminidase and Polymerase Inhibitors in Nude Mice Infected With Influenza Virus.The Journal of infectious diseases · 2018Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Neuraminidase inhibitors (NAIs) play a major role for managing influenza virus infections. The widespread oseltamivir resistance among 2007-2008 seasonal A(H1N1) viruses and community outbreaks of oseltamivir-resistant A(H1N1)pdm09 strains highlights the need for additional anti-influenza virus agents. Laninamivir is a novel long-lasting NAI that has demonstrated in vitro activity against influenza A and B viruses, and its prodrug (laninamivir octanoate) is in phase II clinical trials in the United States and other countries. Currently, little information is available on the mechanisms of resistance to laninamivir. In this study, we first performed neuraminidase (NA) inhibition assays to determine the activity of laninamivir against a set of influenza A viruses containing NA mutations conferring resistance to one or many other NAIs. We also generated drug-resistant A(H1N1) and A(H3N2) viruses under in vitro laninamivir pressure. Laninamivir demonstrated a profile of susceptibility that was similar to that of zanamivir. More specifically, it retained activity against oseltamivir-resistant H275Y and N295S A(H1N1) variants and the E119V A(H3N2) variant. In vitro, laninamivir pressure selected the E119A NA substitution in the A/Solomon Islands/3/2006 A(H1N1) background, whereas E119K and G147E NA changes along with a K133E hemagglutinin (HA) substitution were selected in the A/Quebec/144147/2009 A(H1N1)pdm09 strain. In the A/Brisbane/10/2007 A(H3N2) background, a large NA deletion accompanied by S138A/P194L HA substitutions was selected. This H3N2 variant had altered receptor-binding properties and was highly resistant to laninamivir in plaque reduction assays. Overall, we confirmed the similarity between zanamivir and laninamivir susceptibility profiles and demonstrated that both NA and HA changes can contribute to laninamivir resistance in vitro.
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