A new study shows that a novel antiviral compound is effective against the highly pathogenic H5N1 avian influenza virus, including oseltamivir (Tamiflu)-resistant strains, according to scientists from Japan, Vietnam, Indonesia, and the University of Wisconsin-Madison. The research, published February 26 in the open-access journal PLoS Pathogens, suggests that the prodrug CS-8958 is a promising alternative antiviral for prevention and treatment of H5N1 influenza.
Antiviral drugs are a primary countermeasure against human influenza viruses, including H5N1 avian influenza virus ("bird flu"). Emerging strains resistant to existing drugs, particularly oseltamivir, pose a threat and make the development of alternate antivirals a pressing public health issue. The novel neuraminidase inhibitor R-125489 and its prodrug CS-8958 have previously demonstrated potent activity against seasonal influenza viruses in animal studies.
Working with mice, the researchers found that a single intranasal dose of CS-8958 given two hours after infection with H5N1 influenza virus resulted in a higher survival rate and lower virus levels than a standard five-day course of oseltamivir. CS-8958 was also effective against highly pathogenic and oseltamivir-resistant strains of H5N1 virus. In addition to its therapeutic benefit, CS-8958 also protected mice against lethal H5N1 infection when given seven days before infection with the virus.
While follow-up studies will be needed to confirm the applicability of the findings to humans, the authors conclude that "CS-8958 is highly effective for the treatment and prophylaxis of infection with H5N1 influenza viruses, including oseltamivir-resistant mutants."
FINANCIAL DISCLOSURE: This work was supported by ERATO (Japan Science and Technology Agency), by a grant-in-aid for Specially Promoted Research from the Ministries of Education, Culture, Sports, Science, and Technology, by grants-in-aid from Health, Labor, and Welfare of Japan, by a Contract Research Fund for the Program of Founding Research Centers for Emerging and Reemerging Infectious Diseases, and by research funds from Daiichi-Sankyo, Co., Ltd. The funding bodies had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
COMPETING INTERESTS: YK has received speaker's honoraria from Chugai Pharmaceuticals, Novartis, Diichi-Sankyo, Toyama Chemical, Wyeth, and GlaxoSmithKline; grant support from Chugai Pharmaceuticals, Daiichi Sankyo Pharmaceutical, and Toyama Chemical; and is a founder of FluGen.
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CITATION: Kiso M, Kubo S, Ozawa M, Le QM, Nidom CA, et al. (2010) Efficacy of the New Neuraminidase Inhibitor CS-8958 against H5N1 Influenza Viruses. PLoS Pathog 6(2): e1000786. doi:10.1371/journal.ppat.1000786
Professor Yoshihiro Kawaoka
University of Wisconsin-Madison
Department of Pathobiological Sciences
University of Wisconsin-Madison
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