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.
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http://dx.doi.org/10.1016/j.antiviral.2016.12.011 | DOI Listing |
Euro Surveill
December 2024
Research Center for Influenza and Respiratory Viruses, National Institute of Infectious Diseases, Tokyo, Japan.
An outbreak of influenza A(H1N1)pdm09 viruses exhibiting cross-resistance to oseltamivir and peramivir occurred in Yokohama, Japan, in September 2024. Among 24 students in a class, 11 were diagnosed with influenza or influenza-like illness, and viruses harbouring the NA H275Y and HA Q210H substitutions were isolated from four. Deep sequencing analysis confirmed the clonal spread of these mutants.
View Article and Find Full Text PDFViruses
July 2024
Unit 17 Influenza and Other Respiratory Viruses, Department 1 Infectious Diseases, Robert Koch-Institute, 13353 Berlin, Germany.
The unexpected emergence of oseltamivir-resistant A(H1N1) viruses in 2008 was facilitated in part by the establishment of permissive secondary neuraminidase (NA) substitutions that compensated for the fitness loss due to the NA-H275Y resistance substitution. These viruses were replaced in 2009 by oseltamivir-susceptible A(H1N1)pdm09 influenza viruses. Genetic analysis and screening of A(H1N1)pdm09 viruses circulating in Germany between 2009 and 2024 were conducted to identify any potentially synergistic or resistance-associated NA substitutions.
View Article and Find Full Text PDFExpert Opin Pharmacother
July 2024
Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory of Drug Metabolism Research and Evaluation, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Introduction: Since the coronavirus disease 2019-mandated social distancing policy has been lifted worldwide, the circulation of influenza is expected to resume. Currently, oseltamivir is approved as the first-line agent for influenza prevention and treatment.
Areas Covered: This paper reviews the updated evidence in the pharmacology, resistance mechanisms, clinical pharmacy management, and real-world data on oseltamivir for influenza.
J Mol Diagn
July 2024
Department of Molecular Biology, Princeton University, Princeton, New Jersey; Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey; Omenn-Darling Bioengineering Institute, Princeton University, Princeton, New Jersey; Department of Chemistry, Princeton University, Princeton, New Jersey. Electronic address:
Antiviral Res
July 2024
Laboratorio de Virología, Centro de Investigaciones Regionales Dr, Hideyo Noguchi, Universidad Autónoma de Yucatán, 97225, Yucatan, Mexico. Electronic address:
The most widely used class of antivirals available for Influenza treatment are the neuraminidase inhibitors (NAI) Oseltamivir and Zanamivir. However, amino acid (AA) substitutions in the neuraminidase may cause reduced inhibition or high antiviral resistance. In Mexico, the current state of knowledge about NAI susceptibility is scarce, in this study we report the results of 14 years of Influenza surveillance by phenotypic and genotypic methods.
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