The emergence and global spread of the 2009 pandemic H1N1 influenza virus reminds us that we are limited in the strategies available to control
influenza infection.
Vaccines are the best option for the prophylaxis and control of a pandemic; however, the lag time between virus identification and
vaccine distribution exceeds 6 months and concerns regarding
vaccine safety are a growing issue leading to vaccination refusal. In the short-term,
antiviral therapy is vital to control the spread of
influenza. However, we are currently limited to four licensed anti-
influenza drugs: the
neuraminidase inhibitors
oseltamivir and
zanamivir, and the M2
ion-channel inhibitors
amantadine and
rimantadine. The value of
neuraminidase inhibitors was clearly established during the initial phases of the 2009 pandemic when
vaccines were not available, i.e. stockpiles of
antivirals are valuable. Unfortunately, as
drug-resistant variants continue to emerge naturally and through selective pressure applied by use of
antiviral drugs, the efficacy of these drugs declines. Because we cannot predict the strain of influenza virus that will cause the next epidemic or pandemic, it is important that we develop novel anti-
influenza drugs with broad reactivity against all strains and subtypes, and consider moving to multiple
drug therapy in the future. In this article we review the experimental data on investigational
antiviral agents undergoing clinical trials (parenteral
zanamivir and
peramivir, long-acting
neuraminidase inhibitors and the polymerase inhibitor
favipiravir [T-705]) and experimental
antiviral agents that target either the virus (the haemagglutinin inhibitor
cyanovirin-N and thiazolides) or the host (fusion
protein inhibitors [
DAS181],
cyclo-oxygenase-2 inhibitors and
peroxisome proliferator-activated receptor agonists).