The antiviral drug peramivir could offer people significant protection from
pandemic influenza caused by a mutation of the avian H5N1 virus, researchers have claimed.
Investigators at St. Jude Children’s Research Hospital in Memphis demonstrated the drug’s ability to prote
ct mice from a virulent strain of H5N1. Notably, they report a 100% survival rate in animals receiving daily intramuscular injections of peramivir.
The drug blocks the ability of influenza viruses to use an enzyme called neuraminidase. This prevents the release of new virus particles and limit
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their spread from one infected cell to another. The St. Jude team studied different approaches to treating infected mice byvarying the duration of treatment, route of administration (intramuscular injections alone versus intramuscular injections followed by oral administration), and frequency of administration.
In all cases, the investigators gave peramivir to mice one hour after nasally
administering a lethal Vietnam strain of H5N1 influenza virus. They found 100% survival among 10 infected mice given intramuscular injections of peramivir daily for eight days. The drug also inhibited replication of the virus in the lung, brain and spleen.
Early treatment is ‘key’
They say that the key to the high survival rate was treating the infected mice within 24 hours after infection with H5N1 and continuing the treatment for eight days. “Peramivir should be given as soon as H5N1 infection is suspected, since onset of symptoms in infected humans can be delayed,” said Dr David Boltz of the Infectious Diseases department at St. Jude. “The drug could also be given as a preventive measure during an outbreak to decrease the risk of infection,” he said.
In contrast, a single intramuscular injection resulted in a 40% survival
rate, while two intramuscular injections increased the rate to 60%. The
single intramuscular injection did not completely inhibit H5N1 virus
replication in the lungs and spleen, but did decrease the spread of virus to
the brain. “Our findings support the use of peramivir during a pandemic, and we are currently studying the emergence of H5N1 variants that are resistant to this drug and may occur in the course of treatment,” said another of the research team, Dr Natalia Ilyushina.
Details of the study were presented at the 20th International Conference on Antiviral Research in Palm Springs, California. The research was supported by National Institute of Allergy and Infectious Diseases, the US Public Health Service, BioCryst Pharmaceuticals and ALSAC.
Influenza experts have already warned that new anti-flu drugs might be needed to fight H5N1-related viruses as evidence of resistance to existing medicines emerges. In January, PharmaTimes World News reported that two people had died in Egypt after being infected by an H5N1 strain that was resistant to Roche’s key oral antiviral drug Tamiflu (oseltamivir) – also a neuraminidase inhibitor.
The resistant strain, known as 294S, first emerged in Vietnam in 2005. However, events in Egypt provided the first evidence of it spreading beyond Asia, World Health Organization experts said.
One expert, Dr Anne Moscona of Weill Cornell Medical College, told the New York Times that doctors might have to consider switching to a cocktail of drugs as first-line treatment, as is done with AIDS medications and sometimes with antibiotics.
