BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//CERN//INDICO//EN
BEGIN:VEVENT
SUMMARY:Structure-based Development of Inhibitors of HCV NS5b
DTSTART;VALUE=DATE-TIME:20141120T063000Z
DTEND;VALUE=DATE-TIME:20141120T080000Z
DTSTAMP;VALUE=DATE-TIME:20260711T052730Z
UID:indico-contribution-722@events01.synchrotron.org.au
DESCRIPTION:Speakers: Craig Morton (St Vincent's Institute for Medical Res
 earch)\nInfection by the Hepatitis C virus (HCV) affects in the order of 1
 50 million people world-wide with more than 300\,000 dying each year from 
 HCV-induced liver disease. The RNA-dependent RNA-polymerase of HCV\, NS5b\
 , is widely accepted as an ideal candidate for therapeutic development due
  to the lack of an equivalent enzymatic activity in normal human cells and
  the absolute dependence of viral replication on NS5b. Here we present the
  results of a fragment-based discovery program carried out as part of our 
 research into NS5b inhibitors. A number of fragments identified as NS5b li
 gands through STD-NMR analysis\, as well as structural analogues of these 
 fragments\, were soaked into crystals of HCV NS5b and the structures of th
 e complexes determined. On the basis of the proximity of one of these comp
 ounds to the primer grip site of the enzyme\, hybrid compounds linking the
  compound and a known inhibitor were designed and synthesised. These hybri
 d compounds were found to be potent inhibitors of the HCV replicon and NS5
 b enzymatic assay and were shown crystallographically to bind in the prime
 r grip site in precisely the orientation predicted from modelling.\n\nhttp
 s://events01.synchrotron.org.au/event/3/contributions/722/
LOCATION: NCSS Exhibition Area
URL:https://events01.synchrotron.org.au/event/3/contributions/722/
END:VEVENT
END:VCALENDAR