Drugs in Development for Influenza

Abstract

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 six months and concerns of 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 (NA) inhibitors oseltamivir and zanamivir, and M2 ion-channel inhibitors amantadine and rimantadine. The value of NA 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. Here we review the experimental data on investigational antiviral agents undergoing clinical trials [parenteral zanamivir and peramivir; long acting NA inhibitors (LANI), and polymerase inhibitor T-705], experimental antiviral agents that target either the virus [hemagglutinin (HA) inhibitor Cyanovirin-N and Thiazolides] or the host [fusion protein inhibitor (DAS181), Cox-2 inhibitors and PPAR agonists].

Prevention of influenza by targeting host receptors using engineered proteins

“…Significant effort is being devoted to developing new vaccine approaches to influenza (23,24), new inhibitors of viral targets (25), and novel strategies targeted at host factors (26,27). One host-targeted strategy is to suppress the availability of sialic acid receptors on the respiratory tract epithelium that are recognized by the influenza virus HA glycoprotein.…”

T-705 (Favipiravir) Induces Lethal Mutagenesis in Influenza A H1N1 Viruses In Vitro

“…Progress in the development of influenza therapeutics accelerated after the emergence of highly pathogenic H5N1 influenza viruses in 1997 and the novel H1N1 pandemic influenza strain in 2009 (3,4). New strategies for the use of the currently licensed agents, including alternative forms of delivery and combination therapy with other drugs, are being explored (5). In addition, several novel antiviral compounds with different anti-influenza mechanisms are in various clinical phases of development.…”

Pinanamine Is a Promising Lead Compound against Influenza A Virus: Evidence from <i>in Vitro</i> and <i>in Vivo</i> Efficacy Compared to Amantadine

“…8) Though resistance to both antiviral classes has been increasingly documented globally, 9,10) some studies have indicated that amantadine-sensitive reassortant H1N1 virus became predominant in Japan during the 2007-2008 season. 11) Therefore, the M2 inhibitor appears to be potential in treating patients infected with these amantadine-sensitive viruses.…”