The influenza virus represents a permanent global health threat because it circulates not only within but
also between numerous host populations, thereby frequently causing unexpected outbreaks in animals and humans
with a generally unpredictable course of disease and epidemiology. Conventional influenza therapy is directed
against the viral neuraminidase protein, which promotes virus release from infected cells, and the viral ion channel
M2, which facilitates viral uncoating. However, these drugs, albeit effective, have a major drawback: their targets
are of a highly variable sequence. As a consequence, the virus can readily acquire resistance by mutating the drug
targets. Indeed, most seasonal A/H1N1 viruses and the 2009 H1N1 virus are resistant to M2 inhibitors, and a significant
proportion of the seasonal A/H1N1 viruses are resistant to the neuraminidase inhibitor oseltamivir. Development
of new effective drugs for treatment of disease during the regular influenza seasons and the possible influenza pandemic represents
an important goal. The results presented here point out natural products as a promising source of low toxic and widely accessible
drug candidates for treatment of the influenza disease. Natural products combined with new therapeutic targets and drug repurposing
techniques, which accelerate development of new drugs, serve as an important platform for development of new influenza therapeutics.
Keywords: Influenza disease, natural compounds, therapeutic targets, drug development, drug repurposing, influenza hemagglutinin inhibitors,
influenza NS1 inhibitors, influenza polymerase inhibitors.
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