Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis C virus (HCV) develops persistent infection in most infected patients, and eventually cause chronic hepatitis, liver cirrhosis and then hepatocellular carcinoma. The combination therapy of PEG-IFN and ribavirin improves the efficacy in many patients, while it does not lead to sufficient achievements in genotype1b patients. To invent new anti-HCV reagent, we focused on host factors which HCV take advantage of in its life-cycle. We identified serine palmitoyltransferase inhibitor as anti-HCV reagent through high-through put screenig using HCV replicon cells. Moreover, we evaluate the anti-HCV effect of SPT-inhibitor in vivo with humanized chimeric mice. SPT-inhibitor led to rapid decline in serum HCV-RNA of about 1-2log within 8 day, futhermore the combination therapy of SPT-inhibitor and PEG-IFN achieved about 3log reduction in serum HCV-RNA. At last, we investigated the mechanism of anti-HCV effect of SPT-inhibitor. It has been reported that sphingolipids and cholesterol compose the lipid raft, in which the replication of HCV occur. We investigated the influence of SPT-inhibitor to lipid rafts by analysing the detergent resistant membrane (DRM). The analysis proved that SPT inhibitor got HCV RNA dependent RNA polymerase (NS5B) to move to detergent soluble fraction from DRM, and Biacore analysis indicated the binding of sphingomyelin to NS5B. These results suggested SPT inhibitor got NS5B to release from replication complex.
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PMID:[Suppression of hepatitis C virus with the reagent targetting host factors]. 1937 99

Hepatitis C virus (HCV) persists chronically in most infected patients, eventually causing chronic hepatitis, liver cirrhosis, and in some cases hepatocellular carcinoma. The combination therapy of PEG-IFN and ribavirin improves efficacy in many patients, although it does not lead to sufficient achievements in genotype 1b patients. To aid in invention of new anti-HCV reagents, we focused on host factors that contributed to HCV lifecycle. We identified serine palmitoyltransferase inhibitor as an anti-HCV reagent through high-throughput screening using HCV replicon cells. We investigated the mechanism of anti-HCV effect of SPT inhibitor. It has been reported that sphingolipids and cholesterol compose the lipid raft where replication of HCV occurs. We investigated the influence of SPT inhibitor to lipid rafts by analyzing the detergent-resistant membrane (DRM). The analysis showed that SPT inhibitor moved HCV RNA-dependent RNA polymerase (NS5B) to detergent-soluble fraction from DRM, and Biacore analysis indicated binding of sphingomyelin to NS5B. These results suggest that SPT inhibitor disrupts the interaction between NS5B and sphingomyelin. Moreover, we evaluated the anti-HCV effect of SPT inhibitor in vivo with humanized chimeric mice. SPT inhibitor led to rapid decline in serum HCV-RNA of about 1-2 log within 8 days. Furthermore, combination therapy of SPT inhibitor and PEG-IFN achieved about 3 log reduction in serum HCV-RNA.
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PMID:[Suppression of hepatitis C virus (HCV) replication with serine palmitoyltransferase inhibitor]. 2011 37