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 Hepatitis C virus (HCV) NS3/4A Serine protease is an important drug target for treating patients with hepatitis C virus. However, its amino acid mutations, particularly A156G, commonly lead to the rapid emergence of drug resistance. Bosiprevir, simiprevir, and viniprevir drugs approved by the FDA show distinct resistance profiles against the HCV NS3/4A protease. In order to show the behavior of each of these drugs in the interaction with the protease in the wild type and A156G mutant, molecular dynamics simulation and binding free energy calculations were performed. MMPBSA-based binding free energy calculations showed that the binding affinity of each of the drugs in the interaction with NS3/4A protease in the wild type is significantly more than the interaction with the protease in the A156G mutant state. Free energy landscape (FEL) calculations revealed that in the presence of each of the drugs, more basins of conformations are formed. We hope that our data can provide useful insights for the design of a new effective inhibitory drug for the treatment of patients with the hepatitis C virus.
 

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Objective: Hepatitis C virus (HCV) is considered to be a worldwide health problem. In most cases, HCV infection becomes chronic and may proceed to fibrosis, cirrhosis, and hepatocellular carcinoma. Many pathological effects in cells may occur by viral proteins. The purpose of this study is to evaluate the effect of the HCV core protein on cells to induction of the fibrogenesis process. Methods: We use the LX-2 cell line that originated from hepatic stellate cells. Plasmid which expressed HCV core protein was transfected to the cells. After 72 h, RNA was extracted and treated with DNase, followed by synthesis of cDNA. Positive control cells were treated with the leptin fibrotic hormone. We used real-time PCR to measure and statistically analyze α-SMA gene expression. Results: The HCV core protein significantly increased α-SMA gene expression (p<0.05). There was more α-SMA gene expression in cells treated with leptin compared to cells treated with the HCV core protein. Conclusion: HCV infection is an impressive factor in the development of chronic hepatitis to hepatic fibrogenesis. The HCV core protein can induce a fibrogenesis process in HCV infection.  

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Hepatitis C virus (HCV) is a common cause of liver cirrhosis and hepatocellular carcinoma (HCC) worldwide. The combination of ribavirin and peg-interferon, as standard treatment for HCV infection, seems very promising. Many studies have revealed that despite following standard HCV treatment, a high proportion of HCV genotypes 1 and 4 poorly attain (42% to 46%) the SVR condition, whereas it is somehow easier for HCV genotypes 2 and 3 (76%-82%). Overall, genotypes 1 and 4 antiviral therapies must be continued up to one year to achieve SVR, whereas in individuals infected with genotypes 2 and 3 must continue therapy for six months. Since 2011, direct-acting antiviral agents (DAA) have been introduced that target the HCV-encoded proteins which are vital for replication of the virus. The first generation of DAA, telaprevir, in combination with peg-interferon and ribavirin, more efficiently inhibits replication of genotype 1. Although the level of DAA SVR rate is high, the new treatment has some undesirable adverse effects. Micro-RNAs (miRNAs), as the new HCV drug approach, open a new insight into the treatment of non-responder HCV patients. Altered expression of miRNAs is involved in the aspects of HCV infection and HCC. In the current review, we attempt to better understand the HCV life cycle, liver miRNAs, and their role in this viral infection.