ArticleProceedings of the National Academy of Sciences of the United States of America2012
Polymer-attached zanamivir inhibits synergistically both early and late stages of influenza virus infection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed, 48 citations in OpenAlex.
- Advances in nanotechnology application in biosafety materials: A crucial response to COVID-19 pandemic.Biosafety and health · 2022Review
- Syk Facilitates Influenza A Virus Replication by Restraining Innate Immunity at the Late Stage of Viral Infection.Journal of virology · 2022Article
- Antivirals Targeting the Neuraminidase.Cold Spring Harbor perspectives in medicine · 2022Review
- Multiscale Simulations Examining Glycan Shield Effects on Drug Binding to Influenza Neuraminidase.Biophysical journal · 2020Article
- Polymers in the Medical Antiviral Front-Line.Polymers · 2020Review
- Development of effective anti-influenza drugs: congeners and conjugates - a review.Journal of biomedical science · 2019Review
- Antiviral strategies against influenza virus: towards new therapeutic approaches.Cellular and molecular life sciences : CMLS · 2014Review
- Zanamivir conjugated to poly-L-glutamine is much more active against influenza viruses in mice and ferrets than the drug itself.Pharmaceutical research · 2014Article
- Conjugation to polymeric chains of influenza drugs targeting M2 ion channels partially restores inhibition of drug-resistant mutants.Journal of pharmaceutical sciences · 2013Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Covalently conjugating multiple copies of the drug zanamivir (ZA; the active ingredient in Relenza) via a flexible linker to poly-l-glutamine (PGN) enhances the anti-influenza virus activity by orders of magnitude. In this study, we investigated the mechanisms of this phenomenon. Like ZA itself, the PGN-attached drug (PGN-ZA) binds specifically to viral neuraminidase and inhibits both its enzymatic activity and the release of newly synthesized virions from infected cells. Unlike monomeric ZA, however, PGN-ZA also synergistically inhibits early stages of influenza virus infection, thus contributing to the markedly increased antiviral potency. This inhibition is not caused by a direct virucidal effect, aggregation of viruses, or inhibition of viral attachment to target cells and the subsequent endocytosis; rather, it is a result of interference with intracellular trafficking of the endocytosed viruses and the subsequent virus-endosome fusion. These findings both rationalize the great anti-influenza potency of PGN-ZA and reveal that attaching ZA to a polymeric chain confers a unique mechanism of antiviral action potentially useful for minimizing drug resistance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.