Avian influenza A (H5N1) infection: targets and strategies for chemotherapeutic intervention.
In an avian flu pandemic, which drugs could be used to treat or prevent infection with influenza A (H5N1) virus? Foremost are the viral neuraminidase inhibitors oseltamivir and zanamivir, which have already been used to treat human influenza A (H1N1 and H3N2) and B virus infections. The use of the M2 ion channel blockers amantadine and rimantadine is compounded by the rapid development of drug resistance. Although formally approved for other indications (i.e. treatment of hepatitis C), ribavirin and pegylated interferon might also be useful for controlling avian flu. Combined use of the currently available drugs should be taken into account and attempts should be made to develop new strategies directed at unexplored targets such as the viral proteins hemagglutinin, the viral polymerase (and endonuclease) and the non-structural protein NS1. As has been shown for other viral infections, RNA interference could be a powerful means with which to suppress the replication of avian H5N1.
De Clercq
Erik
E
Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium. erik.declercq@rega.kuleuven.be
Neyts
Johan
J
D000998:Antiviral Agents / Q000494:pharmacology*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D004359:Drug Therapy, Combination; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects* / Q000502:physiology; D007251:Influenza, Human / Q000188:drug therapy; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D034622:RNA Interference; D014763:Viral Matrix Proteins / Q000037:antagonists & inhibitors; D014779:Virus Replication; D000086082:Viroporin Proteins
D000998:Antiviral Agents; D012321:DNA-Directed RNA Polymerases; D007168:IMP Dehydrogenase; D009439:Neuraminidase; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins