Generation of Selective High Affinity Ligands to Block CD81-Large Extracellular Loop: Hepatitis C Virus-E2 Glycoprotein Interaction

Abstract

Background and Aims: HCV infects around 3.3% of the world population. The standard of care HCV treatment (Peginterferon/Ribavirin) leads to serious side effects and SVR is <50% in genotype-1 patients. The newly FDA approved protease inhibitors (Telaprevir/Boceprevir) were found to be effective when each is combined with PR giving higher SVR rates in GT-1. However the poor safety profile of TVR and BOC reported in the Week 16 analysis of the French Early Access Program suggest there is still a need for better HCV drugs. Many companies have active programs developing HCV protease and polymerase inhibitors. We are developing drugs to block an earlier step in HCV infection, CD81 mediated invasion. In this study we are developing Selective High Affinity Ligands (SHALs) to target the E2 binding site on CD81 and block their interaction.