The Life Cycle and in silico Elucidation of Non-structural Replicating Proteins of HCV Through a Pharmacoinformatics Approach

Abstract

Background: Hepatitis C virus (HCV) is an enveloped and positive-stranded RNA virus that is a major causative agent of chronic liver diseases worldwide. HCV has become the main cause of liver transplantations and there is no effective drug for all hepatitis genotypes. Elucidation of life cycle and nonstructural proteins of HCV involved in viral replication are the attractive targets for the development of antiviral drugs. Methods: In this work, pharmacoinformatics approaches coupled with docking analyses were applied on HCV nonstructural proteins to identify the novel potential hits and HCV drugs. Molecular docking analyses were carried out on HCV approved drugs followed by the ligand-based pharmacophore generation to screen the antiviral libraries for novel potential hits. Results: Virtual screening technique has made known the top-ranked five novel compounds (ZINC00607900, ZINC03635748, ZINC03875543, ZINC04097464, and ZINC12503102) along with the least binding energy (-8.0 kcal/mol, -6.1 kcal/mol, -7.5 kcal/mol, -7.4 kcal/mol, and -7.3 kcal/mol respectively) and stability with non-structural proteins target. Conclusion: These promising hits exhibited better absorption and ADMET properties as compared to the selected drug molecules. These potential compounds extracted from in silico approach may be significant in drug design and development against Hepatitis and other liver diseases.

Computer-aided drug design against schizophrenia by targeting SP4

“…The ADMET properties analyses of the selected compounds were crossverified and found similar results. The toxicity analyses and the observed toxicity calculations help in the evaluation of different pollutants, metabolites and intermediates [15]. The solubility of water molecules at 25°C was also calculated for the scrutinized compounds and it was observed that all the scrutinized compounds showed water solubility.…”

“…Understanding this link between SP4 and schizophrenia is critical for the development of effective treatments and interventions for this complex mental illness [8]. There has been impressive progress reported in computational drug design and immuno-informatics [9][10][11][12][13][14][15][16][17][18][19][20][21][22] over the last two decades. Various problems in life sciences and biological sciences have been solved by using the different applications and approaches of computational biology [2].…”

In silico elucidation of potential drug targets against oxygenase domain of Human eNOS Dysfunction

“…Various bioinformatics techniques have been utilized to solve numerous biological problems [10]. Progressive improvements have been observed in immunoinformatics [11][12][13][14] and computational drug designing [10,[15][16][17][18][19][20][21][22][23] from last decade. Various problems of biology have been resolved through applying bioinformatics approaches.…”

Computational 3D structure prediction followed by molecular docking to reveal the novel drug targets against ADA

“…The achievement of immuno-informatics research and computerized drug design has significantly increased during the preceding fifteen years. The in silico, bioinformatics, and immunoinformatic techniques have been used to answer numerous biological problems [6][7][8][9][10][11][12][13][14]. The molecular docking analyses were used in the current in silico effort to identify the novel molecules against ADA.…”