Potential Impact of Environmental Pollution by Human Antivirals on Avian Influenza Virus Evolution

SIMPLE SUMMARY: The massive use, often without any real rationale, of antivirals such as Oseltamivir has as a side effect a significant increase in environmental pollution levels. The effect of the spread of these drugs, especially in aquatic basins, has manifested itself in changes in animal behavior with consequent implications for ecological and evolutionary balances. We focused on the effects that can be detected on avian influenza, which today represents one of the most important viral infectious diseases with possible dramatic pandemic repercussions. We evaluated the evolutionary rate of highly pathogenic H5N1 avian influenza strains and a potentially different evolutionary behavior of the H5N1 2.3 viral clade in the presence of environmental pollution by Oseltamivir. ABSTRACT: Antiviral (AV) drugs are the main line of defense against pandemic influenza. However, different administration policies are applied in countries with different stocks of AV drugs. These policies lead to different occurrences of drug metabolites in the aquatic environment, altering animal behavior with evolutionary consequences on viruses. The aim of this study was to investigate the potential impact of environmental pollution by human antivirals, such as oseltamivir carboxylate (OC), on the evolutionary rate of avian influenza. We used NA, HA, NP, and MP viral segments from two groups of neighboring countries sharing migratory routes of wild birds and characterized by different AV stockpiles. BEAST analyses were performed using the uncorrelated lognormal clock evolutionary model and the Bayesian skyline tree prior model. The ratios between the rate of evolution of the NA gene and the HA, NP, and MP segments were considered. The two groups of countries were compared by analyzing the differences in the ratio distributions. Our analyses highlighted a possible different behavior in the evolution of H5N1 2.3 clade viral strains when OC environmental pollution is present. In conclusion, the widespread consumption of antivirals and their presence in wastewater could influence the selective pressure on viruses.