Anti-influenza virus activity of peramivir in mice with single intramuscular injection
| Autor: | Cynthia Parker, Ramanda Upshaw, C. Shane Arnold, Pooran Chand, Shanta Bantia |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Oseltamivir
medicine.drug_class viruses Orthomyxoviridae Drug Evaluation Preclinical Acids Carbocyclic Neuraminidase Cyclopentanes medicine.disease_cause Antiviral Agents Guanidines Injections Intramuscular chemistry.chemical_compound Mice Zanamivir Influenza A Virus H1N1 Subtype Orthomyxoviridae Infections Virology medicine Influenza A virus Animals Pharmacology biology Neuraminidase inhibitor business.industry virus diseases biology.organism_classification respiratory tract diseases Disease Models Animal chemistry biology.protein Peramivir Female Intramuscular injection business medicine.drug |
| Zdroj: | Antiviral research. 69(1) |
| ISSN: | 0166-3542 |
| Popis: | In the event of an influenza outbreak, antivirals including the neuraminidase (NA) inhibitors, peramivir, oseltamivir, and zanamivir may provide valuable benefit when vaccine production is delayed, limited, or cannot be used. Here we demonstrate the efficacy of a single intramuscular injection of peramivir in the mouse influenza model. Peramivir potently inhibits the neuraminidase enzyme N9 from H1N9 virus in vitro with a 50% inhibitory concentration (IC(50)) of 1.3+/-0.4 nM. On-site dissociation studies indicate that peramivir remains tightly bound to N9 NA (t(1/2)>24h), whereas, zanamivir and oseltamivir carboxylate dissociated rapidly from the enzyme (t(1/2)=1.25 h). A single intramuscular injection of peramivir (10mg/kg) significantly reduces weight loss and mortality in mice infected with influenza A/H1N1, while oseltamivir demonstrates no efficacy by the same treatment regimen. This may be due to tight binding of peramivir to the N1 NA enzymes similar to that observed for N9 enzyme. Additional efficacy studies indicate that a single injection of peramivir (2-20mg/kg) was comparable to a q.d.x 5 day course of orally administered oseltamivir (2-20mg/kg/day) in preventing lethality in H3N2 and H1N1 influenza models. A single intramuscular injection of peramivir may successfully treat influenza infections and provide an alternate option to oseltamivir during an influenza outbreak. |
| Databáze: | OpenAIRE |
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