ribavirin brands

Molecular formula: C8H12N4O5

Ribavirin is reported to have several mechanism of actions that lead to inhibition of viral RNA and protein synthesis. After activation by adenosine kinase to ribavirin mono-, di-, and triphosphate metabolites. Ribavirin triphosphate (RTP) is the predominant metabolite which directly inhibits viral mRNA polymerase by binding to the nucleotide binding site of the enzyme. This prevents the binding of the correct nucleotides, leading to a reduction in viral replication or to the production of defective virions. RTP also demonstrates an inhibitory action on viral mRNA guanylyltransferase and mRNA 2′-O-methyltransferase of dengue virus. Inhibition of these enzymes disrupts the posttranslational capping of the 5′ end of viral mRNA through ribavirin being incorporated at the 5′ end in place of guanosine and preventing the cap methylation step. Inhibition of host inosine monophosphate dehydrogenase (IMPDH) and subsequent depletion of GTP pool is proposed to be another mechanism of action of ribavirin. IMPDH catalyzes the rate-limiting step where inosine 5′-monophosphate is converted to xanthine monophosphate during guanosine monophosphate (GMP) synthesis. GMP is later converted to guanosine triphoshpate (GTP). Ribavirin monophosphate mimics inosine 5′-monophosphate and acts as a competitive inhibitor of IMPDH. Inhibited de novo synthesis of guanine nucleotides and decreased intracellular GTP pools leads to a decline in viral protein synthesis and limit replication of viral genomes. Ribavirin acts as a mutagen in the target virus to cause an 'error catastrophe' due to increased viral mutations. RTP pairs with cytidine triphosphate or uridine triphosphate with equal efficiency and to block HCV RNA elongation. It causes premature termination of nascent HCV RNA and increases mutagenesis by producing defective virions. Ribavirin also exerts an immunomodulatory action of the host to the virus by shifting a Th2 response in favor of a Th1 phenotype. Th2 response and production of type 2 cytokines such as IL-4, IL-5, and IL-10 stimulates the humoral response which enhances immunity toward the virus. Ribavirin enhanced induction of interferon-related genes, including the interferon-α receptor, and down-regulation of genes involved in interferon inhibition, apoptosis, and hepatic stellate cell activation in vitro. The exact mechanism of action of the antiviral activity of ribavirin has not been fully elucidated, but the drug appears to exert its antiviral activity by interfering with RNA and DNA synthesis and subsequently inhibiting protein synthesis and viral replication. The antiviral activity of the drug results principally in an intracellular virustatic effect in cells infected with ribavirin sensitive RNA or DNA viruses; however, specific mechanisms of action of the drug may vary depending on the virus. In virus infected cells in vitro, ribavirin generally exhibits a greater affinity for inhibition of viral DNA and RNA synthesis than cellular (host cell) DNA and RNA synthesis. However, in vesicular stomatitis virus infected cells in vitro, the drug appeared to exhibit a greater affinity for inhibition of cellular than viral RNA synthesis. Inhibition of cellular RNA synthesis usually occurs only at in vitro concentrations higher than those necessary for inhibition of cellular DNA synthesis. The antiviral activity of ribavirin appears to depend principally on intracellular conversion of the drug to ribavirin-5'-triphosphate and -monophosphate. Ribavirin-5'-diphosphate exhibits minimal antiviral activity compared with the monophosphate or triphosphate. Ribavirin is readily absorbed across the cellular plasma membrane, probably via a nucleoside transport mechanism. The drug is then converted via cellular enzymes to deribosylated ribavirin (the 1,2,4-triazole-3-carboxamide) and phosphorylated to ribavirin-5'-monophosphate, -diphosphate, and -triphosphate. Phosphorylation of ribavirin occurs principally in virus infected cells, but also occu

Source: PubChem (NCBI) · compound 37542