ArticleAntimicrobial agents and chemotherapy2012
Exacerbation of influenza virus infections in mice by intranasal treatments and implications for evaluation of antiviral drugs.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
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- Targeted recruitment of immune effector cells for rapid eradication of influenza virus infections.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Targeting SOX13 inhibits assembly of respiratory chain supercomplexes to overcome ferroptosis resistance in gastric cancer.Nature communications · 2024Article
- Volume-Associated Clinical and Histopathological Effects of Intranasal Instillation in Syrian Hamsters: Considerations for Infection and Therapeutic Studies.Pathogens (Basel, Switzerland) · 2022Article
- SPINK6 inhibits human airway serine proteases and restricts influenza virus activation.EMBO molecular medicine · 2022Article
- Acute stress-induced change in polysialic acid levels mediated by sialidase in mouse brain.Scientific reports · 2019Article
- Intranasal delivery of adjuvant-free peptide nanofibers elicits resident CD8Journal of controlled release : official journal of the Controlled Release Society · 2018Article
- Inhibiting influenza virus replication and inducing protection against lethal influenza virus challenge through chitosan nanoparticles loaded by siRNA.Drug delivery and translational research · 2018Article
- Identification of a novel small-molecule compound targeting the influenza A virus polymerase PB1-PB2 interface.Antiviral research · 2017Article
- A novel small-molecule inhibitor of influenza A virus acts by suppressing PA endonuclease activity of the viral polymerase.Scientific reports · 2016Article
- Using the Ferret as an Animal Model for Investigating Influenza Antiviral Effectiveness.Frontiers in microbiology · 2016Review
- How to approach and treat viral infections in ICU patients.BMC infectious diseases · 2014Review
- A zanamivir dimer with prophylactic and enhanced therapeutic activity against influenza viruses.The Journal of antimicrobial chemotherapy · 2014Article
- Zanamivir conjugated to poly-L-glutamine is much more active against influenza viruses in mice and ferrets than the drug itself.Pharmaceutical research · 2014Article
- Innate immune protection against infectious diseases by pulmonary administration of a phospholipid-conjugated TLR7 ligand.Journal of innate immunity · 2014Article
- Zanamivir Diminishes Lung Damage in Influenza A Virus-infected Mice by Inhibiting Nitric Oxide Production.In vivo (Athens, Greece)Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Compounds lacking oral activity may be delivered intranasally to treat influenza virus infections in mice. However, intranasal treatments greatly enhance the virulence of such virus infections. This can be partially compensated for by giving reduced virus challenge doses. These can be 100- to 1,000-fold lower than infections without such treatment and still cause equivalent mortality. We found that intranasal liquid treatments facilitate virus production (probably through enhanced virus spread) and that lung pneumonia was delayed by only 2 days relative to a 1,000-fold higher virus challenge dose not accompanied by intranasal treatments. In one study, zanamivir was 90 to 100% effective at 10 mg/kg/day by oral, intraperitoneal, and intramuscular routes against influenza A/California/04/2009 (H1N1) virus in mice. However, the same compound administered intranasally at 20 mg/kg/day for 5 days gave no protection from death although the time to death was significantly delayed. A related compound, Neu5Ac2en (N-acetyl-2,3-dehydro-2-deoxyneuraminic acid), was ineffective at 100 mg/kg/day. Intranasal zanamivir and Neu5Ac2en were 70 to 100% protective against influenza A/NWS/33 (H1N1) virus infections at 0.1 to 10 and 30 to 100 mg/kg/day, respectively. Somewhat more difficult to treat was A/Victoria/3/75 virus that required 10 mg/kg/day of zanamivir to achieve full protection. These results illustrate that treatment of influenza virus infections by the intranasal route requires consideration of both virus challenge dose and virus strain in order to avoid compromising the effectiveness of a potentially useful antiviral agent. In addition, the intranasal treatments were shown to facilitate virus replication and promote lung pathology.
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