Acetylsalicylic acid (ASA) blocks influenza virus propagation via its NF-kappaB-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-kappaB signalling pathway for efficient replication suggesting that this module may be a suitable target for antiviral intervention. Here we examined acetylsalicylic acid (ASA), also known as aspirin, a widely used drug with a well-known capacity to inhibit NF-kappaB. We show that the drug efficiently blocks influenza virus replication in vitro and in vivo in a mechanism involving impaired expression of proapoptotic factors, subsequent inhibition 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.
Mazur
Igor
I
Institute of Molecular Virology, ZMBE, Westfaelische-Wilhelms-University, Von-Esmarch-Street 56, D-48149 Muenster, Germany.
Wurzer
Walter J
WJ
Ehrhardt
Christina
C
Pleschka
Stephan
S
Puthavathana
Pilaipan
P
Silberzahn
Tobias
T
Wolff
Thorsten
T
Planz
Oliver
O
Ludwig
Stephan
S
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001241:Aspirin / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology; D053126:Influenza A Virus, H7N7 Subtype / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000821:virology; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D016328:NF-kappa B; D001241:Aspirin