First report on molecular docking analysis and drug resistance substitutions to approved HCV NS5A and NS5B inhibitors amongst Iranian patients

Abstract

Background NS5A and NS5B proteins of hepatitis C virus (HCV) are the main targets of compounds that directly inhibit HCV infections. However, the emergence of resistance-associated substitutions (RASs) may cause substantial reductions in susceptibility to inhibitors. Methods Viral load and genotyping were determined in eighty-seven naïve HCV-infected patients, and the amplified NS5A and NS5B regions were sequenced by Sanger sequencing. In addition, physicochemical properties, structural features, immune epitopes, and inhibitors-protein interactions of sequences were analyzed using several bioinformatics tools. Results Several amino acid residue changes were found in NS5A and NS5B proteins; however, we did not find any mutations related to resistance to the treatment in NS5B. Different phosphorylation and few glycosylation sites were assessed. Disulfide bonds were identified in both proteins that had a significant effect on the function and structure of HCV proteins. Applying reliable software to predict B-cell epitopes, 3 and 5 regions were found for NS5A and NS5B, respectively, representing a considerable potential to induce the humoral immune system. Docking analysis determined amino acids involved in the interaction of inhibitors and mentioned proteins may not decrease the drug efficiency. Conclusions Strong interactions between inhibitors, NS5A and NS5B proteins and the lack of efficient drug resistance mutations in the analyzed sequences may confirm the remarkable ability of NS5A and NS5B inhibitors to control HCV infection amongst Iranian patients. The results of bioinformatics analysis could unveil all features of both proteins, which can be beneficial for further investigations on HCV drug resistance and designing novel vaccines.

First report of computational protein–ligand docking to evaluate susceptibility to HIV integrase inhibitors in HIV-infected Iranian patients

“…This report defined N, O, and C glycosylation sites and, to the best of our knowledge, the influence of glycosylation on integrase proteins and HIV pathogenesis is not described clearly; thus, experimental studies are needed to elaborate on this matter [ 94 ].…”

Predictors of antiretroviral treatment failure to the first line therapy: a cross-sectional study among Iranian HIV-positive adults

“…The rate of adherence refers to the prescribed dose of drug taken by the patient at a given time [ 5 ]. The adherence categories were considered good, unstable, or poor based on the self-report inventory.…”

“…Infectious diseases with a broad range of clinical complications remain a noteworthy public health concern because they inflict numerous tragedies and great catastrophes in human history in different parts of the world [1][2][3][4][5][6]. Among various infections, HIV is a global crisis and a formidable challenge that has caused widespread epidemics in all countries, including Iran [7][8][9].…”