Surprises from the crystal structure of the hepatitis C virus NS2-3 protease

✍ Scribed by Jerome Gouttenoire; Darius Moradpour; François Penin

• Book ID: 102240575
• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 314 KB
• Volume: 44
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.21449

✦ Synopsis

In this context, a recent study comparing HCV IRES ⅐ 40S and HCV IRES ⅐ 80S structures has demonstrated conformational changes in the IIIabc four-way junction as well as the pseudoknot that could have been induced by eIF3. 16 Higher resolution structures should yield further insight into the interactions of the HCV IRES with eIF3 and 40S and should result in an improved understanding of the molecular mechanisms involved in formation of active 80S ribosomes.

In conclusion, the work by Siridechadilok et al. provides exciting structural insights into a fundamental biological process and an essential step of the HCV life cycle that represents a potential target for antiviral intervention. Understanding of the complex interactions between the HCV IRES and the host cell translation machinery is crucial for the design of compounds intervening at the step of polyprotein translation. Rational design and optimization of small molecules that block the interaction of the HCV IRES with eIF3 or the 40S ribosome may provide a new class of antivirals against hepatitis C.