Therapeutic efficacy of peramivir against H5N1 highly pathogenic avian influenza viruses harboring the neuraminidase H275Y mutation.

Abstract

High morbidity and mortality associated with human cases of highly pathogenic avian influenza (HPAI) viruses, including H5N1 influenza virus, have been reported. The purpose of the present study was to evaluate the antiviral effects of peramivir against HPAI viruses. In neuraminidase (NA) inhibition and virus replication inhibition assays, peramivir showed strong inhibitory activity against H5N1, H7N1 and H7N7 HPAI viruses with sub-nanomolar activity in enzyme assays. In H5N1 viruses containing the NA H275Y mutation, the antiviral activity of peramivir against the variant was lower than that against the wild-type. Evaluation of the in vivo antiviral activity showed that a single intravenous treatment of peramivir (10 mg/kg) prevented lethality in mice infected with wild-type H5N1 virus and also following infection with H5N1 virus with the H275Y mutation after a 5 day administration of peramivir (30 mg/kg). Furthermore, mice injected with peramivir showed low viral titers and low levels of proinflammatory cytokines in the lungs. These results suggest that peramivir has therapeutic activity against HPAI viruses even if the virus harbors the NA H275Y mutation.

• Authors: Masanori Kobayashi, Makoto Kodama, Takeshi Noshi, Ryu Yoshida, Takushi Kanazu, Naoki Nomura, Kosuke Soda, Norikazu Isoda, Masatoshi Okamatsu, Yoshihiro Sakoda, Yoshinori Yamano, Akihiko Sato, Hiroshi Kida
• Journal: Antiviral research (Antiviral Res) Vol. 139 Pg. 41-48 (Mar 2017) ISSN: 1872-9096 [Electronic] Netherlands
• PMID: 28012921 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

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

Topics

• Acids, Carbocyclic
• Animals
• Antiviral Agents (administration & dosage, therapeutic use)
• Cyclopentanes (administration & dosage, therapeutic use)
• Cytokines (immunology)
• Disease Models, Animal
• Guanidines (administration & dosage, therapeutic use)
• Humans
• Influenza A Virus, H5N1 Subtype (drug effects, enzymology, genetics, pathogenicity)
• Influenza A Virus, H7N1 Subtype (drug effects, enzymology)
• Influenza A Virus, H7N7 Subtype (drug effects, enzymology)
• Influenza, Human (drug therapy)
• Lung (immunology, virology)
• Mice
• Mutation
• Neuraminidase (antagonists & inhibitors, genetics)
• Orthomyxoviridae Infections (drug therapy, virology)
• Viral Load (drug effects)
• Virus Replication (drug effects)