Therapeutic targets for influenza – perspectives in drug development

Abstract

Since new and dangerous influenza virus strains, such as H5N1 “avian flu” and more recently the swine-origin H1N1 “swine flu”, are constantly evolving, the need for effective anti-influenza drugs is pressing. It is becoming clear that the emergence of drug-resistant viruses will be a major potential problem in future efforts to control influenza virus infection. Moreover, development of vaccines against new influenza strains takes several months, and their production capacity is limited. Thus, new classes of anti-influenza drugs are highly sought after. This review focuses mainly on novel strategies, including targeting viral entry into host cells, inhibition of viral transcription and genome replication, and targeting of the NS1 influenza protein. Another approach involves viral RNA silencing by siRNAs or by antisense oligonucleotides. Inhibitors of viral neuraminidase have been the most successful approach in influenza virus breakdown to date. Viral maturation can also be blocked by inhibition of hemagglutinin-processing cellular proteinases. Compounds modifying the host cell immune response have also been reported. Design of specific compounds universally active against all viral variants with a reduced potential for the emergence of drug-resistant mutants is the main challenge in anti-influenza drug development, and the goals in this field are discussed here. A review with 140 references.