Biomaterial Database

Picornaviral 3C protease inhibitors and the dual 3C protease/coronaviral 3C-like protease inhibitors. 2010

Hui-Min Wang, and Po-Huang Liang

Kaohsiung Medical University, Center of Excellence for Environmental Medicine, Department of Fragrance and Cosmetic Science, Kaohsiung 80708, Taiwan, ROC. davidw@kmu.edu.tw

BACKGROUND Picornaviruses are small non-enveloped RNA viruses with genomic RNA of 7500 - 8000 nucleotides, whereas coronaviruses (CoV) are RNA viruses with larger genome of 27 - 32 kb. Both types of viruses translate their genetic information into polyprotein precursors that are processed by virally encoded 3C proteases (3C(pro)) and 3C-like proteases (3CL(pro)), respectively, to generate functional viral proteins. The most studied human rhinoviruses (HRV) belonging to picornaviridae family are the main etiologic agents of the common cold. Due to lack of effective drugs, 3C(pro) has served as an excellent target for anti-viral intervention and considerable efforts have been made in the development of inhibitors. Interestingly, the inhibitors of 3C(pro) cannot inhibit 3CL(pro) potently without modification due to subtle differences in their active-site structures, but a group of common inhibitors against 3C(pro) and 3CL(pro) were found recently. METHODS The inhibitors against 3C(pro) reported in the literatures and patents, with a focus on those inhibiting HRV and the dual picornaviral 3C(pro)/coronaviral 3CL(pro) inhibitors, are summarized in this review. RESULTS Readers will rapidly gain an overview of the individual and dual 3C(pro) inhibitors and the structural basis for discriminating them. CONCLUSIONS In the future, more selective potent inhibitors against each protease and dual inhibitors against both proteases can be further developed to treat the diseases caused by picornaviruses and CoV.

UI	MeSH Term	Description	Entries
D010330	Patents as Topic	Works about exclusive legal rights or privileges applied to inventions, plants, etc.	Trademarks,Patents as Topics,Trademark
D010849	Picornaviridae	A family of small RNA viruses comprising some important pathogens of humans and animals. Transmission usually occurs mechanically. There are nine genera: APHTHOVIRUS; CARDIOVIRUS; ENTEROVIRUS; ERBOVIRUS; HEPATOVIRUS; KOBUVIRUS; PARECHOVIRUS; RHINOVIRUS; and TESCHOVIRUS.	Avihepatovirus,Pasivirus,Picornaviruses,Rosavirus,Sapelovirus,Senecavirus,Sicinivirus,Tremovirus,Avihepatoviruses,Pasiviruses,Rosaviruses,Sapeloviruses,Senecaviruses,Siciniviruses,Tremoviruses
D010850	Picornaviridae Infections	Virus diseases caused by the PICORNAVIRIDAE.	Picornavirus Infections,Infections, Picornaviridae,Infections, Picornavirus,Infection, Picornaviridae,Infection, Picornavirus,Picornaviridae Infection,Picornavirus Infection
D011480	Protease Inhibitors	Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).	Antiprotease,Endopeptidase Inhibitor,Endopeptidase Inhibitors,Peptidase Inhibitor,Peptidase Inhibitors,Peptide Hydrolase Inhibitor,Peptide Hydrolase Inhibitors,Peptide Peptidohydrolase Inhibitor,Peptide Peptidohydrolase Inhibitors,Protease Antagonist,Protease Antagonists,Antiproteases,Protease Inhibitor,Antagonist, Protease,Antagonists, Protease,Hydrolase Inhibitor, Peptide,Hydrolase Inhibitors, Peptide,Inhibitor, Endopeptidase,Inhibitor, Peptidase,Inhibitor, Peptide Hydrolase,Inhibitor, Peptide Peptidohydrolase,Inhibitor, Protease,Inhibitors, Endopeptidase,Inhibitors, Peptidase,Inhibitors, Peptide Hydrolase,Inhibitors, Peptide Peptidohydrolase,Inhibitors, Protease,Peptidohydrolase Inhibitor, Peptide,Peptidohydrolase Inhibitors, Peptide
D003546	Cysteine Endopeptidases	ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000086042	3C Viral Proteases	A class of cysteine proteases which play an essential role in VIRUS REPLICATION. They cleave precursor viral POLYPROTEINS to produce functional proteins and enzymes. In addition, they cleave certain host cell proteins such as EUKARYOTIC INITIATION FACTOR-4G.	3C Proteases,3C Proteinases,3C-like Viral Proteases,3Cpro Proteinases,Proteases, 3C,Proteases, 3C-like Viral,Proteinases, 3C,Viral Proteases, 3C-like
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000998	Antiviral Agents	Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.	Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D014764	Viral Proteins	Proteins found in any species of virus.	Gene Products, Viral,Viral Gene Products,Viral Gene Proteins,Viral Protein,Protein, Viral,Proteins, Viral