Targets of anti-influenza chemotherapy other than neuraminidase and proton pump.
Antiviral chemotherapy for influenza started with treatment with amantadine and then progressed with finding the clinical efficacy of neuraminidase (NA) inhibitors. Beside amantadine and NA inhibitors, there are several compounds that attack novel targets of influenza virus (FluV) replication. Binding and penetration of FluV to cell membrane are important stages in the process of virus replication, and several compounds that inhibit these functions have been reported, although most of them have yet to be examined for clinical use. A polyoxometalate (PM523) was shown to be potent inhibitor of FluV A, respiratory syncytial virus and measles virus, and was shown to inhibit membrane fusion between FluV envelope and the cellular membrane. Strains of virus with acquired resistance to PM523 had mutations in the amino acids substrates in HA1 head, and amino acid changes occurred in the interface peptide of the trimers of HA. Cap formation of FluV-encoded mRNA is unique; it utilizes 5'-mGpppXm of host mRNA. Several substances which inhibit the cap formation of FluV (they are inhibitors of PB2 enzyme activity of FluV) are introduced and reviewed in this article. A metabolic product of ribavirn, 1,2,4 triazole carboxamide (T-CONH2) is inhibitory for FluV A growth in vitro. Peroral administration of TCONH2 also showed therapeutic effect in an experimental mouse infection model of FluV A as well as ribavirin. TCONH2 seems to be less toxic than ribavirin for mice, and may be useful as alternative chemotherapy of ribavirin. Other anti-FluV substances that have been reported to be effective for FluV infection in the mouse are discussed with respect to the possibility of their clinical potential.
Shigeta
S
S
Fukushima Medical University, School of Medicine 1, Hikarigaoka, Japan. sshigeta@fmu.ac.jp
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects; D051379:Mice; D009439:Neuraminidase / Q000187:drug effects*; D009975:Orthomyxoviridae / Q000187:drug effects*; D017494:Proton Pumps / Q000187:drug effects*; D012367:RNA, Viral / Q000187:drug effects / Q000235:genetics; D012254:Ribavirin / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D000998:Antiviral Agents; D017494:Proton Pumps; D012367:RNA, Viral; D012254:Ribavirin; D009439:Neuraminidase