Peroxisome proliferator-activated receptor and AMP-activated protein kinase agonists protect against lethal influenza virus challenge in mice

Abstract

Background: A novel influenza A (H1N1) virus was isolated from humans in North America and has developed into the first pandemic of the 21st century. Reports of a global shortage of antiviral drugs, the evolution of drug-resistant influenza virus variants, and a 6-month delay in vaccine availability underline the need to develop new therapeutics that may be widely distributed during future pandemics. Methods: In an effort to discover alternatives to the conventional therapeutic strategies available, we screened several classes of immunomodulatory agents possessing the potential to mitigate the effects of influenza virus-induced immunopathology. Results: Here, we provide preliminary evidence that two classes of drugs, peroxisome proliferator-activated receptor agonists and AMP-activated protein kinase agonists, provide protection in mice infected with highly pathogenic and pandemic strains of influenza virus. Conclusions: The extensive production in the developed world, combined with the significant degree of protection described here, establishes these drugs as a potential therapeutic option that may be broadly implemented to combat serious disease caused by future influenza epidemics or pandemics. © 2010 Blackwell Publishing Ltd.