A ligand structure based shape similarity approach was used towards the development of new HCV translation inhibitors targeting the viral internal ribosomal entry site (IRES) RNA. The structure of a known inhibitor of the HCV IRES subdomain IIa RNA was used as query molecule in an in silico shape similarity screening against a small molecule database. The output molecules that resembled the overall shape of the query molecule were analyzed following a set of guidelines for selection. The selected scaffolds were further modified to include desired features guided by the ligand-bound crystal structure. The preliminary screening of some of the designed molecules shows promising results. Given the conformational flexibility of the RNA targets, this shape similarity based approach may have general applicability towards the RNA targeting ligand discovery.

Shape similarity based approach towards the development of new HCV translation inhibitors

244th National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.