3.3.8 IRES Inhibitors

The internal ribosome initiation site (IRES) is a part of the hepatitis C virus that is found in different genotypes. It is an essential part of the replication process, so scientists believe that, by finding an IRES inhibitor, there will be a decreased production of the virus. Several companies are working with possible IRES inhibitors.

RiboGene (QuestCor) is currently investigating small molecules for the treatment of hepatitis C, which will inhibit IRES.

RiboTargets RNA Inhibitor is an IRES-inhibitor, still in lab studies. The company’s work is being done by a multidiscipline consortium funded by a Framework 5 award from the European Commision ( www.ribotargets.com).

OSI Pharmaceuticals is working on an anti-IRES inhibitor designated as I70, which showed antiviral activity against HCV in the XTL HCV-Trimera mouse model ( www.hepnet.com/hepc/Mont98/index.html).

Anadys Pharmaceuticals has collected much data about the structure and function of the IRES target and has developed novel screening assays for the identification of antiviral drug candidates ( http://www.anadyspharma.com/home.asp   PTC Therapeutics “is currently using its TRC technologies to identify small molecules that specifically inhibit the ability of HCV mRNA to function.” (http://www.ptcbio.com/big/indexhome.html

Schering-Plough is using artificial ribozymes to target HCV IRES in vitro and in vivo (Curr Opin Mol Ther. 2001 Jun;3(3):278-87).