Human rhinovirus 3C protease as a potential target for the development of antiviral agents.
As the major cause of the common cold in children and adults, human rhinoviruses (HRVs) are a group of small single-stranded positive-sense RNA viruses. HRVs translate their genetic information into a polyprotein precursor that is mainly processed by a virally encoded 3C protease (3Cpro) to generate functional viral proteins and enzymes. It has been shown that the enzymatic activity of HRV 3Cpro is essential to viral replication. The 3Cpro is distinguished from most other proteases by the fact that it has a cysteine nucleophile but with a chymotrypsin-like serine protease folding. This unique protein structure together with its essential role in viral replication made the 3Cpro an excellent target for antiviral intervention. In recent years, considerable efforts have been made in the development of antiviral compounds targeting this enzyme. To further facilitate the design of potent 3C protease inhibitors for therapeutic use, this review summarizes the biochemical and structural characterization conducted on HRV 3C protease along with the recent progress on the development of 3C protease inhibitors.
Wanga
Q May
QM
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. qmwang@lilly.com
Chen
Shu-Hui
SH
D000086042:3C Viral Proteases; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D012229:Rhinovirus / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics
D000998:Antiviral Agents; D015853:Cysteine Proteinase Inhibitors; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases