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BioAssay: AID 330323

Inhibition of hepatitis C virus replication in Huh7-K2040 cells in presence of delipidated fetal calf serum medium by RT-PCR

Hepatitis C virus (HCV) is a single-stranded positive-sense RNA virus of the Flaviviridae family. HCV-infected hepatocytes are known to produce reactive oxygen species (ROS), which initiate lipid peroxidation, a reaction that converts polyunsaturated fatty acids, such as arachidonate, into reactive carbonyls that inactivate proteins. To study the effect of lipid peroxidation on HCV replication, more ..
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Active(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Active(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 330323
Data Source: ChEMBL (478349)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-25
Modify Date: 2014-05-14

Data Table ( Complete ):           View Active Data    View All Data
BioActive Compound: 1
Description:
Title: Inhibition of hepatitis C virus replication by peroxidation of arachidonate and restoration by vitamin E.

Abstract: Hepatitis C virus (HCV) is a single-stranded positive-sense RNA virus of the Flaviviridae family. HCV-infected hepatocytes are known to produce reactive oxygen species (ROS), which initiate lipid peroxidation, a reaction that converts polyunsaturated fatty acids, such as arachidonate, into reactive carbonyls that inactivate proteins. To study the effect of lipid peroxidation on HCV replication, we administered arachidonate to Huh7 cells that harbor an HCV replicon (Huh7-K2040 cells). After incubation in medium supplemented with arachidonate but deprived of lipid-soluble antioxidants, the cellular amount of malondialdehyde (MDA), a product of lipid peroxidation, increased markedly in Huh7-K2040 cells but not in parental Huh7 cells that do not harbor an HCV replicon. This increase was followed by a sharp reduction (>95%) in HCV RNA. Both of these events were prevented when cells were treated with vitamin E, a lipid-soluble antioxidant. After prolonged incubation of Huh7-K2040 cells with arachidonate in the absence of lipid-soluble antioxidants, the amount of MDA decreased after the reduction in the amount of HCV RNA. Thus, in the presence of arachidonate and in the absence of lipid-soluble antioxidants, HCV replication induces lipid peroxidation that reduces the amount of HCV RNA. Our results provide a mechanism for the previous observation that polyunsaturated fatty acids inhibit HCV replication [Kapadia SB, Chisari FV (2005) Proc Natl Acad Sci USA 102:2561-2566], and they suggest that these agents may be effective in inhibiting HCV replication in vivo.
(PMID: 18003907)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Putative Target:

ChEMBL Target ID: 50643
Target Type: ORGANISM
Pref Name: Hepatitis C virus
Organism: Hepatitis C virus
Tax ID: 11103
Confidence: Target assigned is non-molecular
Relationship Type: Non-molecular target assigned
Categorized Comment
Assay Type: Functional

Assay Data Source: Scientific Literature

BAO: Assay Format: organism-based format

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
2IC50 activity commentIC50 activity commentString
3IC50 standard flagIC50 standard flagInteger
4IC50 qualifierIC50 qualifierString
5IC50 published valueIC50 published valueFloatμM
6IC50 standard valueIC50 standard valueFloatnM

* Activity Concentration.

Data Table (Concise)
Data Table ( Complete ):     View Active Data    View All Data
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