Biomaterial Database

[Non-hydrolysable analogs of inorganic pyrophosphate as inhibitors of hepatitis C virus RNA-dependent RNA-polymerase]. 2012

D V Ianvarev, and A N Korovina, and N N Usanov, and S N Kochetkov

Inorganic pyrophosphate (PPi) is a product of the polymerization reaction catalyzed by DNA- and RNA-polymerases. We have synthesized a number of novel non-hydrolysable PPi analogues, some of them have demonstrated inhibition of polymerization reaction catalyzed by hepatitis C virus RNA-dependent RNA-polymerase (NS5B). A new pharmacophore has been developed based on non-hydrolysable methylene-diphosphonate backbone. Structure-activity relationship analysis of 12 bisphosphonates is presented and structural features crucial for the ability of molecule to inhibit NS5B polymerase activity are ascertained.

UI	MeSH Term	Description	Entries
D011756	Diphosphates	Inorganic salts of phosphoric acid that contain two phosphate groups.	Diphosphate,Pyrophosphate Analog,Pyrophosphates,Pyrophosphate Analogs,Analog, Pyrophosphate
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006526	Hepatitis C	INFLAMMATION of the LIVER in humans caused by HEPATITIS C VIRUS, a single-stranded RNA virus. Its incubation period is 30-90 days. Hepatitis C is transmitted primarily by contaminated blood parenterally and is often associated with transfusion and intravenous drug abuse. However, in a significant number of cases, the source of hepatitis C infection is unknown.	Hepatitis, Viral, Non-A, Non-B, Parenterally-Transmitted,Parenterally-Transmitted Non-A, Non-B Hepatitis,PT-NANBH,Parenterally Transmitted Non A, Non B Hepatitis
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
D012324	RNA-Dependent RNA Polymerase	An enzyme that catalyses RNA-template-directed extension of the 3'- end of an RNA strand by one nucleotide at a time, and can initiate a chain de novo. (Enzyme Nomenclature, 1992, p293)	Nucleoside-Triphosphate:RNA Nucleotidyltransferase (RNA-directed),RNA Replicase,RNA-Dependent RNA Replicase,RNA-Directed RNA Polymerase,RNA Dependent RNA Polymerase,RNA Dependent RNA Replicase,RNA Directed RNA Polymerase,RNA Polymerase, RNA-Dependent,RNA Polymerase, RNA-Directed,RNA Replicase, RNA-Dependent,Replicase, RNA,Replicase, RNA-Dependent RNA
D012367	RNA, Viral	Ribonucleic acid that makes up the genetic material of viruses.	Viral RNA
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D016174	Hepacivirus	A genus of FLAVIVIRIDAE causing parenterally-transmitted HEPATITIS C which is associated with transfusions and drug abuse. Hepatitis C virus is the type species.	Hepatitis C virus,Hepatitis C-Like Viruses,Hepaciviruses,Hepatitis C Like Viruses,Hepatitis C viruses,Hepatitis C-Like Virus
D017361	Viral Nonstructural Proteins	Proteins encoded by a VIRAL GENOME that are not structural components of VIRUS PARTICLES. Some of these proteins may play roles within the infected cell during VIRUS REPLICATION or act in regulation of virus replication or VIRUS ASSEMBLY.	Nonstructural Proteins, Viral,NS Proteins, Viral,Viral NS Proteins,Viral Non-Structural Proteins,Viral Nonstructural Protein,Viral Nonstructural Proteins NS1,Viral Nonstructural Proteins NS2,Nonstructural Protein, Viral,Viral Non Structural Proteins