Applications of computer-aided approaches in the development of hepatitis C antiviral agents

References

• Weiser BM, Tellinghuisen TL. Structural biology of the hepatitis C virus proteins. Drug Discov Today Technol. 2012;9:e195–e204.
   Google Scholar
• Houghton M. Discovery of the hepatitis C virus. Liver Int. 2009;29:82–88.
   PubMed Web of Science ®Google Scholar
• World Health Organization. Hepatitis C 2016 [ cited 2016 July]. Available from: http://www.who.int/mediacentre/factsheets/fs164/en/.
   Google Scholar
• Choo QL, Kuo G, Weiner AJ, et al. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989;244:359–362.
   PubMed Web of Science ®Google Scholar
• Friedman RM, Contente S. Treatment of hepatitis C infections with interferon: a historical perspective. Hepat res treat. 2010;2010:323926.
   Google Scholar
• McHutchison JG, Gordon SC, Schiff ER, et al. Interferon Alfa-2b alone or in combination with Ribavirin as initial treatment for chronic hepatitis C. N Engl J Med. 1998;339:1485–1492.
   PubMed Web of Science ®Google Scholar
• Kozlowski A, Milton Harris J. Improvements in protein PEGylation: pegylated interferons for treatment of hepatitis C. J Control Release. 2001;72:217–224.
   PubMed Web of Science ®Google Scholar
• Poordad F, Dieterich D. Treating hepatitis C: current standard of care and emerging direct-acting antiviral agents. J Viral Hepat. 2012;19:449–464.
   PubMed Web of Science ®Google Scholar
• Foster GR, Pianko S, Brown A, et al. Efficacy of sofosbuvir plus Ribavirin with or without peginterferon-alfa in patients with hepatitis C Virus genotype 3 infection and treatment-experienced patients with cirrhosis and hepatitis C virus genotype 2 infection. Gastroenterology. 2015;149:1462–1470.
   PubMed Web of Science ®Google Scholar
• McConachie SM, Wilhelm SM, Kale-Pradhan PB. New direct-acting antivirals in hepatitis C therapy: a review of sofosbuvir, ledipasvir, daclatasvir, simeprevir, paritaprevir, ombitasvir and dasabuvir. Expert Rev Clin Pharmacol. 2016;9:287–302.
   PubMed Web of Science ®Google Scholar
• U. S. Food Drug Administration. FDA approves Epclusa for treatment of chronic hepatitis C virus infection 2016[ cited 2016 28 June]. Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm508915.htm.
   Google Scholar
• Rosenthal ES, Graham CS. Price and affordability of direct-acting antiviral regimens for hepatitis C virus in the United States. Infect Agent Cancer. 2016;11:24.
   PubMed Web of Science ®Google Scholar
• FFdC E, Teodorico CR, Carlton AT, et al. Computer-assisted analysis of the interactions of macrocyclic inhibitors with wild type and mutant D168A hepatitis C virus NS3 serine protease. Lett Drug Des Discov. 2006;3:17–28.
   Web of Science ®Google Scholar
• Ontoria JM, Di Marco S, Conte I, et al. The design and enzyme-bound crystal structure of indoline based peptidomimetic inhibitors of hepatitis C virus NS3 protease. J Med Chem. 2004;47:6443–6446.
   PubMed Web of Science ®Google Scholar
• Wei H-Y, Lu C-S, Lin T-H. Exploring the P2 and P3 ligand binding features for Hepatitis C virus NS3 protease using some 3D QSAR techniques. J Mol Graph Model. 2008;26:1131–1144.
   PubMed Web of Science ®Google Scholar
• Xue W, Wang M, Jin X, et al. Understanding the structural and energetic basis of inhibitor and substrate bound to the full-length NS3/4A: insights from molecular dynamics simulation, binding free energy calculation and network analysis. Mol Biosyst. 2012;8:2753–2765.
   PubMed Web of Science ®Google Scholar
• Lin MV, King LY, Chung RT. Hepatitis C virus–associated cancer. Annu Rev Pathol. 2015;10:345–370.
   PubMed Web of Science ®Google Scholar
• Penin F, Dubuisson J, Rey FA, et al. Structural biology of hepatitis C virus. Hepatology. 2004;39:5–19.
   PubMed Web of Science ®Google Scholar
• Ashfaq UA, Javed T, Rehman S, et al. An overview of HCV molecular biology, replication and immune responses. Virol J. 2011;8:1–10.
   PubMed Web of Science ®Google Scholar
• Hundt J, Li Z, Liu Q. Post-translational modifications of hepatitis C viral proteins and their biological significance. World J Gastroenterol. 2013;19:8929–8939.
   PubMed Web of Science ®Google Scholar
• Khaliq S, Jahan S, Hassan S. Hepatitis C virus p7: molecular function and importance in hepatitis C virus life cycle and potential antiviral target. Liver Int. 2011;31:606–617.
   PubMed Web of Science ®Google Scholar
• Marcotrigiano J. Progress on new hepatitis C virus targets: NS2 and NS5A. In: Sussman JL, Spadon P, editors. From molecules to medicines: structure of biological macromolecules and its relevance in combating new diseases and bioterrorism. Dordrecht: Springer Netherlands; 2009. p. 121–138.
   Google Scholar
• Sklan EH, Glenn JS. HCV NS4B: from obscurity to central stage. In: Tan SL, editor. Hepatitis C Viruses: genomes and molecular biology. Norfolk (UK): Horizon Bioscience; 2006.
   Google Scholar
• Wong KA, Worth A, Martin R, et al. Characterization of hepatitis C virus resistance from a multiple-dose clinical trial of the novel NS5A inhibitor GS-5885. Antimicrob Agents Chemother. 2013;57:6333–6340.
   PubMed Web of Science ®Google Scholar
• DeMarini DJ, Johnston VK, Konduri M, et al. Intracellular hepatitis C virus RNA-dependent RNA polymerase activity. J Virol Methods. 2003;113:65–68.
   PubMed Web of Science ®Google Scholar
• Lesburg CA, Cable MB, Ferrari E, et al. Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site. Nat Struct Mol Biol. 1999;6:937–943.
   Google Scholar
• Sesmero E, Thorpe IF. Using the hepatitis C virus RNA-dependent RNA polymerase as a model to understand viral polymerase structure, function and dynamics. Viruses. 2015;7:3974–3994.
   PubMed Web of Science ®Google Scholar
• Barakat KH, Law J, Prunotto A, et al. Detailed computational study of the active site of the hepatitis C viral RNA polymerase to aid novel drug design. J Chem Inf Model. 2013;53:3031–3043.
   PubMed Web of Science ®Google Scholar
• Ohno T, Lau JY. The “gold-standard,” accuracy, and the current concepts: hepatitis C virus genotype and viremia. Hepatology. 1996;24:1312–1315.
   PubMed Web of Science ®Google Scholar
• Simmonds P, Bukh J, Combet C, et al. Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology. 2005;42:962–973.
   PubMed Web of Science ®Google Scholar
• Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon Alfa-2a plus Ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975–982.
   PubMed Web of Science ®Google Scholar
• Meeprasert A, Hannongbua S, Rungrotmongkol T. Key binding and susceptibility of NS3/4A serine protease inhibitors against hepatitis C virus. J Chem Inf Model. 2014;54:1208–1217.
   PubMed Web of Science ®Google Scholar
• Butkiewicz NJ, Wendel M, Zhang R, et al. Enhancement of hepatitis C virus NS3 proteinase activity by association with NS4A-specific synthetic peptides: identification of sequence and critical residues of NS4A for the cofactor activity. Virology. 1996;225:328–338.
   PubMed Web of Science ®Google Scholar
• Koch JO, Lohmann V, Herian U, et al. In vitroStudies on the activation of the hepatitis C virus NS3 proteinase by the NS4A cofactor. Virology. 1996;221:54–66.
   PubMed Web of Science ®Google Scholar
• Arthitaya M, Thanyada R, Mai Suan L, et al. In silico screening for potent inhibitors against the NS3/4A protease of hepatitis C virus. Curr Pharm Des. 2014;20:3465–3477.
   PubMed Web of Science ®Google Scholar
• Romano KP, Ali A, Royer WE, et al. Drug resistance against HCV NS3/4A inhibitors is defined by the balance of substrate recognition versus inhibitor binding. Proceedings of the National Academy of Sciences. 2010;107:20986–20991.
   Google Scholar
• Barbato G, Cicero DO, Nardi MC, et al. The solution structure of the N-terminal proteinase domain of the hepatitis C virus (HCV) NS3 protein provides new insights into its activation and catalytic mechanism1. J Mol Biol. 1999;289:371–384.
   PubMed Web of Science ®Google Scholar
• Shiryaev SA, Thomsen ER, Cieplak P, et al. New details of HCV NS3/4A proteinase functionality revealed by a high-throughput cleavage assay. Plos One. 2012;7:e35759.
   Google Scholar
• Kim JL, Morgenstern KA, Lin C, et al. Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide. Cell. 1996;87:343–355.
   PubMed Web of Science ®Google Scholar
• Abian O, Vega S, Jl N, et al. Conformational stability of hepatitis C virus NS3 protease. Biophys J. 2010;99:3811–3820.
   PubMed Web of Science ®Google Scholar
• Thai KM, Dong QH, Nguyen TTL, et al. Computational approaches for the discovery of novel hepatitis C virus NS3/4A and NS5B inhibitors In: Information resources management A, editor. Oncology: breakthroughs in research and practice.Hershey, PA, USA: IGI Global; 2017. 482–518.
   Google Scholar
• Johansson A, Hubatsch I, Åkerblom E, et al. Inhibition of hepatitis C virus NS3 protease activity by product-based peptides is dependent on helicase domain. Biorg Med Chem Lett. 2001;11:203–206.
   PubMed Web of Science ®Google Scholar
• Frecer V, Kabeláč M, De Nardi P, et al. Structure-based design of inhibitors of NS3 serine protease of hepatitis C virus. J Mol Graph Model. 2004;22:209–220.
   PubMed Web of Science ®Google Scholar
• De Francesco R, Steinkühler C. structure and function of the hepatitis C virus NS3-NS4A serine proteinase. In: Hagedorn CH, Rice CM, editors. The hepatitis C viruses. Berlin, Heidelberg: Springer Berlin Heidelberg; 2000. p. 149–169.
   Google Scholar
• Shu-Hui C, Jason L, Yvonne Y, et al. P1 and P1; optimization of [3,4]-bicycloproline P2 incorporated tetrapeptidyl α-ketoamide based HCV protease inhibitors. Lett Drug Des Discov. 2005;2:118–123.
   Web of Science ®Google Scholar
• Saalau-Bethell SM, Woodhead AJ, Chessari G, et al. Discovery of an allosteric mechanism for the regulation of HCV NS3 protein function. Nat Chem Biol. 2012;8:920–925.
   PubMed Web of Science ®Google Scholar
• Xue W, Yang Y, Wang X, et al. Computational study on the inhibitor binding mode and allosteric regulation mechanism in hepatitis C virus NS3/4A protein. Plos One. 2014;9:e87077.
   Google Scholar
• Kaushik-Basu N, Bopda-Waffo A, Talele TT, et al. Identification and characterization of coumestans as novel HCV NS5B polymerase inhibitors. Nucleic Acids Res. 2008;36:1482–1496.
   PubMed Web of Science ®Google Scholar
• Beaulieu PL. CHAPTER 8 design and development of NS5B polymerase non-nucleoside inhibitors for the treatment of hepatitis C virus infection. In: Manoj C. Desai and Nicholas A. (eds). Successful strategies for the discovery of antiviral drugs: the royal society of chemistry. Cambridge UK:The Royal Society of Chemistry; 2013:248–294.
   Google Scholar
• De Francesco R, Carfí A. Advances in the development of new therapeutic agents targeting the NS3-4A serine protease or the NS5B RNA-dependent RNA polymerase of the hepatitis C virus. Adv Drug Del Rev. 2007;59:1242–1262.
   PubMed Web of Science ®Google Scholar
• Bressanelli S, Tomei L, Rey FA, et al. Structural Analysis of the Hepatitis C Virus RNA Polymerase in Complex with Ribonucleotides. J Virol. 2002;76:3482–3492.
   PubMed Web of Science ®Google Scholar
• Qin W, Luo H, Nomura T, et al. Oligomeric interaction of hepatitis C virus NS5B is critical for catalytic activity of RNA-dependent RNA polymerase. J Biol Chem. 2002;277:2132–2137.
   PubMed Web of Science ®Google Scholar
• Tellinghuisen TL, Rice CM. Interaction between hepatitis C virus proteins and host cell factors. Curr Opin Microbiol. 2002;5:419–427.
   PubMed Web of Science ®Google Scholar
• Lambert SM, Langley DR, Garnett JA, et al. The crystal structure of NS5A domain 1 from genotype 1a reveals new clues to the mechanism of action for dimeric HCV inhibitors. Protein Sci. 2014;23:723–734.
   PubMed Web of Science ®Google Scholar
• Kohler JJ, Nettles JH, Amblard F, et al. Approaches to hepatitis C treatment and cure using NS5A inhibitors. Infect Drug Resist. 2014;7:41–56.
   PubMed Web of Science ®Google Scholar
• Elazar M, Cheong KH, Liu P, et al. Amphipathic helix-dependent localization of NS5A mediates hepatitis C virus RNA replication. J Virol. 2003;77:6055–6061.
   PubMed Web of Science ®Google Scholar
• Foster TL, Belyaeva T, Stonehouse NJ, et al. All three domains of the hepatitis C virus nonstructural NS5A protein contribute to RNA binding. J Virol. 2010;84:9267–9277.
   PubMed Web of Science ®Google Scholar
• Macdonald A, Crowder K, Street A, et al. The hepatitis C virus NS5A protein binds to members of the Src family of tyrosine kinases and regulates kinase activity. J Gen Virol. 2004;85:721–729.
   PubMed Web of Science ®Google Scholar
• Tellinghuisen TL, Marcotrigiano J, Rice CM. Structure of the zinc-binding domain of an essential component of the hepatitis C virus replicase. Nature. 2005;435:374–379.
   PubMed Web of Science ®Google Scholar
• Love RA, Brodsky O, Hickey MJ, et al. Crystal structure of a novel dimeric form of NS5A domain I protein from hepatitis C virus. J Virol. 2009;83:4395–4403.
   PubMed Web of Science ®Google Scholar
• Gao M, Nettles RE, Belema M, et al. Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Nature. 2010;465:96–100.
   PubMed Web of Science ®Google Scholar
• Azam SS, Abbasi SW, Batool M. Structure modeling and docking study of HCV NS5B-3a RNA polymerase for the identification of potent inhibitors. Med Chem Res. 2014;23:618–627.
   Web of Science ®Google Scholar
• Talele TT, Arora P, Kulkarni SS, et al. Structure-based virtual screening, synthesis and SAR of novel inhibitors of hepatitis C virus NS5B polymerase. Biorg Med Chem. 2010;18:4630–4638.
   PubMed Web of Science ®Google Scholar
• Li J, Liu X, Li S, et al. Identification of novel small molecules as inhibitors of hepatitis C virus by structure-based virtual screening. Int J Mol Sci. 2013;14:22845–22856.
   Google Scholar
• Li X, Zhang W, Qiao X, et al. Prediction of binding for a kind of non-peptic HCV NS3 serine protease inhibitors from plants by molecular docking and MM-PBSA method. Biorg Med Chem. 2007;15:220–226.
   PubMed Web of Science ®Google Scholar
• Li W, Si H, Li Y, et al. 3D-QSAR and molecular docking studies on designing inhibitors of the hepatitis C virus NS5B polymerase. J Mol Struct. 2016;1117:227–239.
   Web of Science ®Google Scholar
• Subha K, Kumar GR, Rajalakshmi R, et al. a novel strategy for mechanism based computational drug discovery. Biomark Cancer. 2010;2:35–42.
   PubMedGoogle Scholar
• Anwar-Mohamed A, Barakat KH, Bhat R, et al. A human ether-á-go-go-related (hERG) ion channel atomistic model generated by long supercomputer molecular dynamics simulations and its use in predicting drug cardiotoxicity. Toxicol Lett. 2014;230:382–392.
   PubMed Web of Science ®Google Scholar
• Barakat KH, Anwar-Mohamed A, Tuszynski JA, et al. A refined model of the HCV NS5A protein bound to daclatasvir explains drug-resistant mutations and activity against divergent genotypes. J Chem Inf Model. 2015;55:362–373.
   PubMed Web of Science ®Google Scholar
• Barakat KH, Jordheim LP, Perez-Pineiro R, et al. Virtual screening and biological evaluation of inhibitors targeting the XPA-ERCC1 interaction. Plos One. 2012;7:e51329.
   PubMed Web of Science ®Google Scholar
• El-Labbad EM, Ismail MAH, Abou Ei Ella DA, et al. Discovery of novel peptidomimetics as irreversible CHIKV NsP2 protease inhibitors using quantum mechanical-based ligand descriptors. Chem Biol Drug Des. 2015;86:1518–1527.
   PubMed Web of Science ®Google Scholar
• Kalyaanamoorthy S, Chen Y-P-P. Quantum polarized ligand docking investigation to understand the significance of protonation states in histone deacetylase inhibitors. J Mol Graph Model. 2013;44:44–53.
   PubMed Web of Science ®Google Scholar
• Kalyaanamoorthy S, Chen Y-P-P. A steered molecular dynamics mediated hit discovery for histone deacetylases. Phys Chem Chem Phys. 2014;16:3777–3791.
   PubMed Web of Science ®Google Scholar
• Berger C, Romero-Brey I, Radujkovic D, et al. Daclatasvir-like inhibitors of NS5A block early biogenesis of hepatitis C virus-induced membranous replication factories, independent of RNA replication. Gastroenterology. 2014;147:1094–105.e25.
   PubMed Web of Science ®Google Scholar
• Ascher DB, Wielens J, Nero TL, et al. Potent hepatitis C inhibitors bind directly to NS5A and reduce its affinity for RNA. Sci Rep. 2014;4:4765.
   PubMed Web of Science ®Google Scholar
• Ganesan A, Coote ML, Barakat K. Molecular dynamics-driven drug discovery: leaping forward with confidence. Drug Discov Today. 2017;22:249–269.
   Google Scholar
• Ganesan A, Kumar RS, Kalyaanamoorthy S, et al. AIM-BLAST-AJAX interfaced multisequence blast. Proteomics Insights. 2009;2:9–13.
   Google Scholar
• FFdC E, Karina SM, Teodorico CR. QSAR and docking studies of HCV NS3 serine protease inhibitors. Med Chem. 2013;9:774–805.
   PubMed Web of Science ®Google Scholar
• Ghasemi JB, Nazarshodeh E, Abedi H. Molecular docking, 2D and 3D-QSAR studies of new indole-based derivatives as HCV-NS5B polymerase inhibitors. J Iranian Chem Soc. 2015;12:1789–1799.
   Web of Science ®Google Scholar
• Kitchen DB, Decornez H, Furr JR, et al. Docking and scoring in virtual screening for drug discovery: methods and applications. Nat Rev Drug Discov. 2004;3:935–949.
   PubMed Web of Science ®Google Scholar
• Yang S-Y. Pharmacophore modeling and applications in drug discovery: challenges and recent advances. Drug Discov Today. 2010;15:444–450.
   PubMed Web of Science ®Google Scholar
• Acharya C, Coop A, Polli JE, et al. Recent advances in ligand-based drug design: relevance and utility of the conformationally sampled pharmacophore approach. Curr Comput Aided Drug Des. 2011;7:10–22.
   PubMed Web of Science ®Google Scholar
• Lewis RA, Wood D. Modern 2D QSAR for drug discovery. Wiley Interdiscip Rev Comput Mol Sci. 2014;4:505–522.
   Web of Science ®Google Scholar
• Clark M, Cramer RD, Jones DM, et al. Comparative molecular field analysis (CoMFA) . 2. Toward its use with 3D-structural databases. Tetrahedron Comput Methodol. 1990;3:47–59.
   Google Scholar
• Klebe G, Abraham U, Mietzner T. Molecular Similarity indices in a comparative analysis (CoMSIA) of drug molecules to correlate and predict their biological activity. J Med Chem. 1994;37:4130–4146.
   PubMed Web of Science ®Google Scholar
• Rafiei H, Khanzadeh M, Mozaffari S, et al. QSAR study of HCV NS5B polymerase inhibitors using the genetic algorithm-multiple linear regression (GA-MLR). Excli J. 2016;15:38–53.
   PubMed Web of Science ®Google Scholar
• Elfiky AA, Elshemey WM. IDX-184 is a superior HCV direct-acting antiviral drug: a QSAR study. Med Chem Res. 2016;25:1005–1008.
   PubMed Web of Science ®Google Scholar
• Worachartcheewan A, Prachayasittikul V, Toropova AP, et al. Large-scale structure-activity relationship study of hepatitis C virus NS5B polymerase inhibition using SMILES-based descriptors. Mol Divers. 2015;19:955–964.
   PubMed Web of Science ®Google Scholar
• Chen J, Zhang L, Guo H, et al. Activity prediction of hepatitis C virus NS5B polymerase inhibitors of pyridazinone derivatives. Chemometrics Intellig Lab Syst. 2014;134:100–109.
   Web of Science ®Google Scholar
• Su L, Li L, Li Y, et al. Simple and accurate approaches to predict the activity of benzothiadiazine derivatives as HCV inhibitors. Med Chem Res. 2012;21:2079–2096.
   Web of Science ®Google Scholar
• Stachulski AV, Pidathala C, Row EC, et al. Thiazolides as novel antiviral agents. 2. Inhibition of hepatitis C virus replication. J Med Chem. 2011;54:8670–8680.
   PubMed Web of Science ®Google Scholar
• Cheng Z, Zhang Y, Zhou C. QSAR Models for phosphoramidate prodrugs of 2′-methylcytidine as inhibitors of hepatitis C virus based on PSO boosting. Chem Biol Drug Des. 2011;78:948–959.
   PubMed Web of Science ®Google Scholar
• Michelle R, Marcus Tullius S, Mauro Vicentini C, et al. Sesquiterpene lactones with anti-hepatitis C virus activity using molecular descriptors. Lett Drug Des Discov. 2012;9:881–890.
   Web of Science ®Google Scholar
• Ke-Xian C, Hai-Ying X, Zu-Guang L. QSAR Analysis of 1,1-dioxoisothiazole and benzo[b]thiophene-1,1-dioxide derivatives as novel inhibitors of hepatitis C virus NS5B polymerase. Acta Chim Slov. 2009;56:684–693.
   Web of Science ®Google Scholar
• Yu H, Fang Y, Lu X, et al. Combined 3D-QSAR, molecular docking, molecular dynamics simulation, and binding free energy calculation studies on the 5-hydroxy-2H-pyridazin-3-one derivatives as HCV NS5B polymerase inhibitors. Chem Biol Drug Des. 2014;83:89–105.
   PubMed Web of Science ®Google Scholar
• Jingyu Z, Youyong L, Huidong Y, et al. Insight into the structural requirements of narlaprevir-type inhibitors of NS3/NS4A protease based on HQSAR and molecular field analyses. Comb Chem High Throughput Screen. 2012;15:439–450.
   PubMed Web of Science ®Google Scholar
• Wadood A, Riaz M, Uddin R, et al. In Silico Identification and Evaluation of Leads for the Simultaneous Inhibition of Protease and Helicase Activities of HCV NS3/4A Protease Using Complex Based Pharmacophore Mapping and Virtual Screening. Plos One. 2014;9:e89109.
   PubMed Web of Science ®Google Scholar
• Wei Y, Li J, Qing J, et al. Discovery of novel hepatitis C virus NS5B polymerase inhibitors by combining random forest, multiple e-pharmacophore modeling and docking. Plos One. 2016;11:e0148181.
   PubMed Web of Science ®Google Scholar
• Svetnik V, Liaw A, Tong C, et al. Random Forest: A classification and regression tool for compound classification and QSAR modeling. J Chem Inf Comput Sci. 2003;43:1947–1958.
   PubMedGoogle Scholar
• Ahmed M, Pal A, Houghton M, et al. A comprehensive computational analysis for the binding modes of hepatitis C virus NS5A inhibitors: the question of symmetry. ACS Infect Dis. 2016;2:872–881.
   PubMed Web of Science ®Google Scholar
• Kerrigan J. Molecular dynamics simulations in drug design. In: Kortagere S, editor. In silico models for drug discovery. Methods in molecular biology. Vol. 993. Totowa, NJ:Humana Press; 2013. p. 95–113.
   Google Scholar
• Tautermann CS, Seeliger D, Kriegl JM. What can we learn from molecular dynamics simulations for GPCR drug design? Comput Struct Biotechnol J. 2015;13:111–121.
   PubMed Web of Science ®Google Scholar
• Barakat K, Mane J, Friesen D, et al. Ensemble-based virtual screening reveals dual-inhibitors for the p53–MDM2/MDMX interactions. J Mol Graph Model. 2010;28:555–568.
   PubMed Web of Science ®Google Scholar
• Barakat K, Tuszynski J. Relaxed complex scheme suggests novel inhibitors for the lyase activity of DNA polymerase beta. J Mol Graph Model. 2011;29:702–716.
   PubMed Web of Science ®Google Scholar
• Kalyaanamoorthy S, Chen Y-P-P. Modelling and enhanced molecular dynamics to steer structure-based drug discovery. Prog Biophys Mol Biol. 2014;114:123–136.
   PubMed Web of Science ®Google Scholar
• Hou T, Wang J, Li Y, et al. Assessing the Performance of the MM/PBSA and MM/GBSA methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations. J Chem Inf Model. 2011;51:69–82.
   PubMed Web of Science ®Google Scholar
• Hou T, Wang J, Li Y, et al. Assessing the performance of the molecular mechanics/poisson boltzmann surface area and molecular mechanics/generalized born surface area methods. II. The accuracy of ranking poses generated from docking. J Comput Chem. 2011;32:866–877.
   PubMed Web of Science ®Google Scholar
• Xu L, Sun H, Li Y, et al. Assessing the Performance of MM/PBSA and MM/GBSA methods. 3. The impact of force fields and ligand charge models. J Phys Chem B. 2013;117:8408–8421.
   PubMed Web of Science ®Google Scholar
• Sun H, Li Y, Tian S, et al. Assessing the performance of MM/PBSA and MM/GBSA methods. 4. Accuracies of MM/PBSA and MM/GBSA methodologies evaluated by various simulation protocols using PDBbind data set. Phys Chem Chem Phys. 2014;16:16719–16729.
   PubMed Web of Science ®Google Scholar
• Sun H, Li Y, Shen M, et al. Assessing the performance of MM/PBSA and MM/GBSA methods. 5. Improved docking performance using high solute dielectric constant MM/GBSA and MM/PBSA rescoring. Phys Chem Chem Phys. 2014;16:22035–22045.
   PubMed Web of Science ®Google Scholar
• Hou T, Li N, Li Y, et al. Characterization of domain–peptide interaction interface: prediction of SH3 domain-mediated protein–protein interaction network in yeast by generic structure-based models. J Proteome Res. 2012;11:2982–2995.
   PubMed Web of Science ®Google Scholar
• Guan Y, Sun H, Li Y, et al. The competitive binding between inhibitors and substrates of HCV NS3/4A protease: A general mechanism of drug resistance. Antiviral Res. 2014;103:60–70.
   PubMed Web of Science ®Google Scholar
• Mortier J, Rakers C, Bermudez M, et al. The impact of molecular dynamics on drug design: applications for the characterization of ligand–macromolecule complexes. Drug Discov Today. 2015;20:686–702.
   PubMed Web of Science ®Google Scholar
• Durrant JD, McCammon JA. Molecular dynamics simulations and drug discovery. BMC Biol. 2011;9:1–9.
   PubMed Web of Science ®Google Scholar
• Mahmoud AH, Elsayed MSA, ElHefnawi M. Structure-based predictive model for some benzimidazole inhibitors of hepatitis C virus NS5B polymerase. Med Chem Res. 2013;22:1866–1883.
   Web of Science ®Google Scholar
• Wu S, Kanda T, Nakamoto S, et al. Hepatitis C virus protease inhibitor-resistance mutations: our experience and review. World J Gastroenterol. 2013;19:8940–8948.
   PubMed Web of Science ®Google Scholar
• Halfon P, Locarnini S. Hepatitis C virus resistance to protease inhibitors. J Hepatol. 2011;55:192–206.
   PubMed Web of Science ®Google Scholar
• Lenz O, Verbinnen T, Lin T-I, et al. In Vitro resistance profile of the hepatitis C virus NS3/4A protease inhibitor TMC435. Antimicrob Agents Chemother. 2010;54:1878–1887.
   PubMed Web of Science ®Google Scholar
• Chen Z-W, Li H, Ren H, et al. Global prevalence of pre-existing HCV variants resistant to direct-acting antiviral agents (DAAs): mining the genBank HCV genome data. Sci Rep. 2016;6:20310.
   PubMed Web of Science ®Google Scholar
• Guan Y, Sun H, Pan P, et al. Exploring resistance mechanisms of HCV NS3/4A protease mutations to MK5172: insight from molecular dynamics simulations and free energy calculations. Mol Biosyst. 2015;11:2568–2578.
   PubMed Web of Science ®Google Scholar
• Soumana DI, Kurt Yilmaz N, Ali A, et al. Molecular and dynamic mechanism underlying drug resistance in genotype 3 hepatitis C NS3/4A protease. J Am Chem Soc. 2016;138:11850–11859.
   PubMed Web of Science ®Google Scholar
• Uengwetwanit T, Robaa D, Sippl W. Analysis of the resistance of hepatitis C virus NS5B polymerase inhibitors via docking and molecular dynamics simulation. Mol Inform. 2015;34:78–83.
   PubMed Web of Science ®Google Scholar
• Xue W, Pan D, Yang Y, et al. Molecular modeling study on the resistance mechanism of HCV NS3/4A serine protease mutants R155K, A156V and D168A to TMC435. Antiviral Res. 2012;93:126–137.
   PubMed Web of Science ®Google Scholar
• Kramer M, Halleran D, Rahman M, et al. Comparative molecular dynamics simulation of hepatitis C virus NS3/4A protease (Genotypes 1b, 3a and 4a) predicts conformational instability of the catalytic triad in drug resistant strains. Plos One. 2014;9:e104425.
   Google Scholar
• Xue W, Jiao P, Liu H, et al. Molecular modeling and residue interaction network studies on the mechanism of binding and resistance of the HCV NS5B polymerase mutants to VX-222 and ANA598. Antiviral Res. 2014;104:40–51.
   PubMed Web of Science ®Google Scholar
• Wang H, Cui W, Guo C, et al. Molecular modeling study on the drug resistance mechanism of NS5B polymerase to TMC647055. Biochem Cell Biol. 2015;94:147–158.
   PubMed Web of Science ®Google Scholar
• Elfiky AA, Elshemey WM, Gawad WA, et al. Molecular modeling comparison of the performance of NS5b polymerase inhibitor (PSI-7977) on prevalent HCV genotypes. Protein J. 2013;32:75–80.
   PubMed Web of Science ®Google Scholar
• De Vivo M, Masetti M, Bottegoni G, et al. role of molecular dynamics and related methods in drug discovery. J Med Chem. 2016;59:4035–4061.
   Web of Science ®Google Scholar
• Bernardi RC, Melo MCR, Schulten K. Enhanced sampling techniques in molecular dynamics simulations of biological systems. Biochim Biophys Acta. 2015;1850:872–877.
   PubMed Web of Science ®Google Scholar
• Rodriguez-Bussey IG, Doshi U, Hamelberg D. Enhanced molecular dynamics sampling of drug target conformations. Biopolymers. 2016;105:35–42.
   PubMed Web of Science ®Google Scholar
• Warshel A, Levitt M. Theoretical studies of enzymic reactions: dielectric, electrostatic and steric stabilization of the carbonium ion in the reaction of lysozyme. J Mol Biol. 1976;103:227–249.
   PubMed Web of Science ®Google Scholar
• Ganesan A, Dreyer J, Wang F, et al. Density functional study of Cu2+-phenylalanine complex under micro-solvation environment. J Mol Graph Model. 2013;45:180–191.
   PubMed Web of Science ®Google Scholar
• Park S, Schulten K. Calculating potentials of mean force from steered molecular dynamics simulations. J Chem Phys. 2004;120:5946–5961.
   PubMed Web of Science ®Google Scholar
• Pan D, Niu Y, Ning L, et al. Computational study on the binding and unbinding mechanism of HCV NS5B with the inhibitor GS-461203 and substrate using conventional and steered molecular dynamics simulations. Chemometrics Intellig Lab Syst. 2016;156:72–80.
   Web of Science ®Google Scholar
• Pan D, Niu Y, Xue W, et al. Computational study on the drug resistance mechanism of hepatitis C virus NS5B RNA-dependent RNA polymerase mutants to BMS-791325 by molecular dynamics simulation and binding free energy calculations. Chemometrics Intellig Lab Syst. 2016;154:185–193.
   Web of Science ®Google Scholar
• Pinheiro AS, Duarte JBC, Alves CN, et al. Virtual screening and molecular dynamics simulations from a bank of molecules of the amazon region against functional NS3-4A protease-helicase enzyme of hepatitis C virus. Appl Biochem Biotechnol. 2015;176:1709–1721.
   PubMed Web of Science ®Google Scholar
• Parks JM, Kondru RK, Hu H, et al. Hepatitis C virus NS5B polymerase: QM/MM calculations show the important role of the internal energy in ligand binding. J Phys Chem B. 2008;112:3168–3176.
   PubMed Web of Science ®Google Scholar
• Zeisel MB, Crouchet E, Baumert TF, et al. Host-targeting agents to prevent and cure hepatitis C virus infection. Viruses. 2015;7:5659–5685.
   PubMed Web of Science ®Google Scholar
• Fazi R, Tintori C, Brai A, et al. Homology model-based virtual screening for the identification of human helicase DDX3 inhibitors. J Chem Inf Model. 2015;55:2443–2454.
   PubMed Web of Science ®Google Scholar
• Yang S, J KR, Lim S, et al. Structure-based discovery of novel cyclophilin A inhibitors for the treatment of hepatitis C virus Infections. J Med Chem. 2015;58:9546–9561.
   PubMed Web of Science ®Google Scholar
• Henriksen NM, Hayatshahi HS, Davis DR, et al. Structural and energetic analysis of 2-aminobenzimidazole inhibitors in complex with the hepatitis C virus IRES RNA using molecular dynamics simulations. J Chem Inf Model. 2014;54:1758–1772.
   PubMed Web of Science ®Google Scholar
• Golebiowski J, Antonczak S, Di-Giorgio A, et al. Molecular dynamics simulation of hepatitis C virus IRES IIId domain: structural behavior, electrostatic and energetic analysis. J Mol Model. 2004;10:60–68.
   PubMed Web of Science ®Google Scholar
• Pérard J, Leyrat C, Baudin F, et al. Structure of the full-length HCV IRES in solution. Nat Commun. 2013;4:1612.
   PubMed Web of Science ®Google Scholar
• Saunders MG, Voth GA. Coarse-graining methods for computational biology. Annu Rev Biophys. 2013;42:73–93.
   PubMed Web of Science ®Google Scholar