Abstract
Hepatitis C virus (HCV) infection is a major worldwide problem causes acute and chronic HCV infection. Current treatment of HCV includes pegylated interferon-α (PEG IFN- α) plus ribavirin (RBV) which has significant side effects depending upon the type of genotype. Currently, there is a need to develop antiviral agents, both from synthetic chemistry and Herbal sources. In the last decade, various novel HCV replication, helicase and entry inhibitors have been synthesized and some of which have been entered in different phases of clinical trials. Successful results have been acquired by executing combinational therapy of compounds with standard regime in different HCV replicons. Even though, diverse groups of compounds have been described as antiviral targets against HCV via Specifically Targeted Antiviral Therapy for hepatitis C (STAT-C) approach (in which compounds are designed to directly block HCV or host proteins concerned in HCV replication), still there is a need to improve the properties of existing antiviral compounds. In this review, we sum up potent antiviral compounds against entry, unwinding and replication of HCV and discussed their activity in combination with standard therapy. Conclusively, further innovative research on chemical compounds will lead to consistent standard therapy with fewer side effects.
Highlights
Hepatitis C virus (HCV) belonging to the family Flaviviridae signifies to be an entire global dilemma which parades the variability of genome translated into six genotypes and more than 80 subtypes
This study offers a basis for the clinical estimation of three-part combination of PEG IFN-a, boceprevir and HCV-796 [26]
Therapeutic drugs against HCV may have the potential to put off the replication complex formation [37], to inhibit host cell kinases [69], to block protein folding pathways [70] and targeting to hormone receptors [71]
Summary
HCV belonging to the family Flaviviridae signifies to be an entire global dilemma which parades the variability of genome translated into six genotypes and more than 80 subtypes. A new series of compounds, acridone derivatives, were tested to measure inhibitory effects of derivatives against NS3 helicase activity of HCV in sub-genomic replicon assay These substituted compounds were investigated for transcription inhibition in-vitro based on the DNA-dependent T7 RNA polymerase. The most active chemical entity, 3, 5, 7-tri [(40-methylpiperazin-10-yl) methyl] tropolone inhibited RNA replication by 50% at an effective concentration (EC50) of 46.9 μM, while the most competent one was 3, 5, 7-tri [(30methylpiperidin-10-yl) methyl] tropolone having EC50 of 35.6 μM These derivatives are the first helicase inhibitors that block replication of HCV with the capability of causing the emergence of resistant mutants [60]. The occurrence of the anti-HCV iridoid aglycone epimers, lamiridosins A/B (1/2), in the primed aqueous extract of Lamium album, have shown the diminution in HCVpp entry due to interruption in the binding of HCV E2 with CD81 receptor [68]. (Structures are cited in figure 4)
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