ArticleJournal of virology2000
The anti-influenza virus agent 4-GU-DANA (zanamivir) inhibits cell fusion mediated by human parainfluenza virus and influenza virus HA.
Article in Journal of virology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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47 citing papers in PubMed, 82 citations in OpenAlex.
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- Kinetic analysis of paramyxovirus-sialoglycan receptor interactions reveals virion motility.PLoS pathogens · 2023Article
- Antiviral Peptides as Anti-Influenza Agents.International journal of molecular sciences · 2022Review
- α2,3-Linked Sialic Acids Are the Potential Attachment Receptor for Shaan Virus Infection in MARC-145 Cells.Microbiology spectrum · 2022Article
- Broad-spectrum Respiratory Virus Entry Inhibitors.Advances in experimental medicine and biology · 2022Article
- Antivirals targeting paramyxovirus membrane fusion.Current opinion in virology · 2021Review
- Human parainfluenza virus evolution during lung infection of immunocompromised individuals promotes viral persistence.The Journal of clinical investigation · 2021Article
- Inhibition of Measles Viral Fusion Is Enhanced by Targeting Multiple Domains of the Fusion Protein.ACS nano · 2021Article
- Parainfluenza virus entry at the onset of infection.Advances in virus research · 2021Article
- Human parainfluenza virus fusion complex glycoproteins imaged in action on authentic viral surfaces.PLoS pathogens · 2020Article
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- Inhibiting Human Parainfluenza Virus Infection by Preactivating the Cell Entry Mechanism.mBio · 2019Article
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- Broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides.Scientific reports · 2017Article
- A dual drug regimen synergistically blocks human parainfluenza virus infection.Scientific reports · 2016Article
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- Influenza A virus uses intercellular connections to spread to neighboring cells.Journal of virology · 2015Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
4-GU-DANA (zanamivir) (as well as DANA and 4-AM-DANA) was found to inhibit the neuraminidase activity of human parainfluenza virus type 3 (HPF3). The viral neuraminidase activity is attributable to hemagglutinin-neuraminidase (HN), an envelope protein essential for viral attachment and for fusion mediated by the other envelope protein, F. While there is no evidence that HN's neuraminidase activity is essential for receptor binding and syncytium formation, we found that 4-GU-DANA prevented hemadsorption and fusion of persistently infected cells with uninfected cells. In plaque assays, 4-GU-DANA reduced the number (but not the area) of plaques if present only during the adsorption period and reduced plaque area (but not number) if added only after the 90-min adsorption period. 4-GU-DANA also reduced the area of plaques formed by a neuraminidase-deficient variant, confirming that its interference with cell-cell fusion is unrelated to inhibition of neuraminidase activity. The order-of-magnitude lower 50% inhibitory concentrations of 4-GU-DANA (and also DANA and 4-AM-DANA) for plaque area reduction and for inhibition in the fusion assay than for reducing plaque number or blocking hemadsorption indicate the particular efficacy of these sialic acid analogs in interfering with cell-cell fusion. In cell lines expressing influenza virus hemagglutinin (HA) as the only viral protein, we found that 4-GU-DANA had no effect on hemadsorption but did inhibit HA2b-red blood cell fusion, as judged by both lipid mixing and content mixing. Thus, 4-GU-DANA can interfere with both influenza virus- and HPF3-mediated fusion. The results indicate that (i) in HPF3, 4-GU-DANA and its analogs have an affinity not only for the neuraminidase active site of HN but also for sites important for receptor binding and cell fusion and (ii) sialic acid-based inhibitors of influenza virus neuraminidase can also exert a direct, negative effect on the fusogenic function of the other envelope protein, HA.
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