Acetylsalicylic acid (ASA) blocks influenza virus propagation via its NF-kappa B-inhibiting activity

Influenza is still one of the major plagues worldwide. The statistical likeliness of a new pandemic outbreak highlights the urgent need for new and amply available antiviral drugs. We and others have shown that influenza virus misuses the cellular IKK/NF-kB signal- ling pathway for efficient replication suggesting that this module may be a suitable target for antiviral inter- vention. Here we examined acetylsalicylic acid (ASA), also known as aspirin, a widely used drug with a well-known capacity to inhibit NF-kB. We show that the drug efficiently blocks influenza virus replication in vitro and in vivo in amechanism involving impaired expression of proapoptotic factors, subsequent inhi- bition of caspase activation as well as block of caspase-mediated nuclear export of viral ribonucleoproteins. As ASA showed no toxic side-effects or the tendency to induce resistant virus variants, existing salicylate-based aerosolic drugs may be suitable as anti-influenza agents. This is the first demonstration that specific targeting of a cellular factor is a suitable approach for anti-influenza virus intervention.