Staying one step ahead of influenza

During the H1N1 outbreak, antiviral drugs offered the only hope against emergent flu strains. Two drug classes: adamantanes (FDA approved in 1966) and neuraminidase inhibitors (oseltamivir, FDA approved in 1999) represent two classes of drugs that target viral an ion channel and a cell surface antigen, respectively, hereby preventing or treating infection.

In an ambitious study, the authors attempt to trace drug resistance against all strains of the flu by using an extensive influenza virus database containing all known genetic sequence information (70,000 complete nucleotide sequences) for influenza strains. Using a phylogenetic approach, authors Vanessa Garcia and Stéphane Aris-Brosou examined the evolutionary history of antiviral drug resistance. "Although the approaches employed in our study are not novel in themselves, the scale of the analyses is unprecedented and allowed us to track in public databases the dynamics of all known mutations involved in drug resistance," reported the senior author.

How does the virus outwit two leading antiviral therapies? Widespread use of these drugs has led to the emergence of drug resistance. Most disconcerting, recent "dual resistance" viruses dodge both drugs, leaving us defenseless against the virus. While adamantane resistance mutations appeared readily, it took 15-38 years after FDA approval to emerge, but emerged 3 times, whereas, the less spontaneous oseltamivir mutations took at most 7 years, serving as a public health cautionary tail. The authors support the judicious use of antiviral drugs as a last line of defense against influenza to avoid the spread of dual resistance, which is already circulating in H1N1 viruses in humans. "Our results also suggest that most of the mutations leading to influenza drug resistance are on the wane, so that recent efforts in controlling drug use are paying off, but we should remain vigilant," commented Stéphane Aris-Brosou.