Triazavirin And Its Derivatives Act As Influenza A Virus Fusion Inhibitors.

PURPOSE: The influenza A virus still remains one of the most dangerous pathogens possessing a high potential for the emergence of pandemic strains. However, there are only a few antivirals which are still effective against this virus. So-called viral fusion inhibitors are considered as a relatively new class of such drugs with a high therapeutic potential.

METHODS

We combined a system for monitoring the fusion of individual virions with lipid membranes, molecular dynamics simulations and measurements of affinity of charged molecules to lipid membranes. This allowed us to determine the mechanism of action of the antiviral drug.

RESULTS

We demonstrated that the additional mode of activity of triazavirin, the azoloazine derivative, passed clinical trials, can be an inhibition of the hemagglutinin of the influenza A virus. Combining experimental and computer approaches, we report a more effective modification of the target molecule than the registered drug triazavirin. Additionally, we suggested screening system, which has a good potential for studying the fusion activity and its inhibition for other viruses and potential antiviral drugs acting on viral fusion proteins.

CONCLUSIONS

We report here triazavirin as a fusion inhibitor and propose a new molecule with high activity against influenza A virus, surpassing those of the triazavirin.