Mathematical model for suppression of subgenomic hepatitis C virus RNA replication in cell culture.
A mathematical model for suppression of the hepatitis C virus RNA replicon replication in Huh-7 cell culture in the presence of potential drugs was built. There was a good agreement between the experimental and theoretical kinetic data for the decrease in the level of viral RNA in the cell in the presence of the competitive HCV NS3 protease inhibitor. Using the model, we verified the estimates for the efficiency of the effect of potential drugs on replication of viral RNA and viral protein processing. It was demonstrated that the tested drugs are most efficient at the replication step of viral RNA. The efficiency of the combined action of real and putative inhibitors target on the host and viral proteins was also studied. It was found that the action of the inhibitor at low concentrations on the host factors considerably enhances the suppressive effect on viral RNA replication in the presence of even the low affine NS3 protease inhibitors. The developed mathematical model may serve as a tool for the evaluation of the efficiency of potential drugs on the HCV genome.
Mishchenko
Elena L
EL
Institute of Cytology and Genetics SB RAS, Lavrentieva Ave., 10, Novosibirsk State University, Pirogova Ave., Novosibirsk 630090, Russia. elmish@bionet.nsc.ru
Bezmaternykh
Kirill D
KD
Likhoshvai
Vitaly A
VA
Ratushny
Alexander V
AV
Khlebodarova
Tamara M
TM
Yu Sournina
Natalia
N
Ivanisenko
Vladimir A
VA
Kolchanov
Nikolai A
NA
D002478:Cells, Cultured / Q000821:virology*; D003198:Computer Simulation; D016679:Genome, Viral / Q000502:physiology*; D016174:Hepacivirus / Q000502:physiology*; D008954:Models, Biological; D012367:RNA, Viral / Q000096:biosynthesis*; D012093:Replicon / Q000502:physiology; D014779:Virus Replication / Q000502:physiology*
D012367:RNA, Viral