A single intramuscular injection of neuraminidase inhibitor peramivir demonstrates antiviral activity against novel pandemic A/California/04/2009 (H1N1) influenza virus infection in mice.

Abstract

New and emerging influenza virus strains, such as the pandemic influenza A (H1N1) virus require constant vigilance for antiviral drug sensitivity and resistance. Efficacy of intramuscularly (IM) administered neuraminidase (NA) inhibitor, peramivir, was evaluated in mice infected with recently isolated pandemic A/California/04/2009 (H1N1, swine origin, mouse adapted) influenza virus. A single IM injection of peramivir (four dose groups), given 1h prior to inoculation, significantly reduced weight loss (p < 0.001) and mortality (p < 0.05) in mice infected with LD90 dose of pandemic A/California/04/2009 (H1N1) influenza virus compared to vehicle group. There was 20% survival in the vehicle-treated group, whereas in the peramivir-treated groups, survival increased in a dose-dependent manner with 60, 60, 90 and 100% survivors for the 1, 3, 10, and 30 mg/kg doses, respectively. Weight loss on day 4 in the vehicle-treated group was 3.4 gm, and in the peramivir-treated groups was 2.1, 1.5, 1.8 and 1.8 g for the 1, 3, 10 and 30 mg/kg dose groups, respectively. In the treatment model, peramivir given 24h after infection as a single IM injection at 50mg/kg dose, showed significant protection against lethality and weight loss. There was 13% survival in the vehicle-treated group while in the peramivir-treated group at 24, 48, and 72 h post infection, survival was 100, 40, and 50%, respectively. Survival in the oseltamivir groups (10 mg/kg/d twice a day, orally for 5 days) was 90, 30 and 20% at 24, 48 and 72 h, respectively. These data demonstrate efficacy of parenterally administered peramivir against the recently isolated pandemic influenza virus in murine infection models.

• Authors: Shanta Bantia, Debra Kellogg, Cynthia Parker, Ramanda Upshaw, Natalia A Ilyushina, Y S Babu
• Journal: Antiviral research (Antiviral Res) Vol. 90 Issue 1 Pg. 17-21 (Apr 2011) ISSN: 1872-9096 [Electronic] Netherlands
• PMID: 21316393 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Acids, Carbocyclic
• Antiviral Agents
• Cyclopentanes
• Guanidines
• peramivir

Topics

• Acids, Carbocyclic
• Animals
• Antiviral Agents (administration & dosage)
• Body Weight
• Cyclopentanes (administration & dosage)
• Disease Models, Animal
• Female
• Guanidines (administration & dosage)
• Influenza A Virus, H1N1 Subtype (drug effects)
• Injections, Intramuscular
• Mice
• Mice, Inbred BALB C
• Orthomyxoviridae Infections (drug therapy, mortality, pathology, virology)
• Rodent Diseases (drug therapy, mortality, pathology, virology)
• Survival Analysis