A theoretical study has been carried out to interpret and support experimental findings regarding inhibition mechanism of HCV NS5b. Twenty-five HCV NS5b inhibitors were docked by QM-Polarized Ligand Docking (QPLD) technique. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods were used to derive 3D-QSAR models for the selected inhibitors. The CoMFA and CoMSIA models show good cross-validated (Q2) and non-cross-validated (R2) coefficients for the suggested inhibitors of 0.43, 0.98 and 0.65, 0.99, respectively. The inhibition mechanism was explored and validated. Details of the interactions between the inhibitors and HCV NS5b are given in terms of steric, electrostatic, hydrophobic, hydrogen bonding fields. Enhancing potency via substitutions at positions, which were explored based on these parameters. A good correlation was found between 3D-QSAR and docking results.
| Published in | Journal of Drug Design and Medicinal Chemistry (Volume 3, Issue 4) |
| DOI | 10.11648/j.jddmc.20170304.11 |
| Page(s) | 49-59 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2017. Published by Science Publishing Group |
QPLD, Docking, 3D-QSAR, CoMFA, CoMSIA, HCV NS5b Inhibitors
| [1] | P. Simmonds, J. Mellor, T. Sakuldamrongpanich, C. Nuchaprayoon, S. Tanprasert, E. C. Holmes, D. B. Smith, Evolutionary analysis of variants of hepatitis C virus found in South-East Asia: comparison with classifications based upon sequence similarity, J. Gen. Virol., 77 (1996) 3013-3024. |
| [2] | S. Ramia, J. Eid-Fares, Distribution of hepatitis C virus genotypes in the Middle East Int. J. Infect. Dis., 10 (2006) 272-277. |
| [3] | J. P. Watson, H. Al-Mardini, S. Awadh, S. Ukabam, C. O. Record, Hepatitis C virus genotypes in a cohort of Middle Eastern patients, Ann. Saudi. Med., 19 (1999) 410-412. |
| [4] | F. Fallahian, A. Najafi, Epidemiology of Hepatitis C in the Middle East, Saudi J. Kidney Dis. Transpl., 22 (2011) 1-9. |
| [5] | A. Craxì, J. Pawlotsky, H. Wedemeyer, K. Bjoro, R. Flisiak, X. Forns, M. Mondelli, M. Peck-Radosavljevic, W. Rosenberg, C. Sarrazin, EASL Clinical Practice Guidelines: Management of hepatitis C virus infection, J. Hepatol., 55 (2011) 245–264. |
| [6] | M. Yahia, Global health: a uniquely Egyptian epidemic, Nature, 474 (2011) S12–S13. |
| [7] | F. El-Zanaty, W. Ann, Egypt Demographic and Health Survey 2008 Cairo, Egypt: Ministry of Health, El-Zanaty Associates, and Macro International, (2009). |
| [8] | B. R. Mauss, W. Sarrazin, Short Guide to Hepatitis C, the Flying Publisher, Bernd Kamps Steinhäuser Verlag, 2011, pp. 128. |
| [9] | M. A. Kamel, Y. A. Ghaffar, M. A. Wasef, M. Wright, L. C. Clark, F. D. Miller, High HCV prevalence in Egyptian Blood donors, Lancet., 340 (1992) 427. |
| [10] | C. Frank, M. K. Mohamed, G. T. Strickland, D. Lavanchy, R. R. Arthur, L. S. Magder, T. El Khoby, Y. Abdel-Wahab, E. Aly Ohn, W. Anwar, I. Sallam, The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt, Lancet 355 (2000) 887–891. |
| [11] | M. Karmochkine, F. Carrat, O. Dos Santos, P. Cacoub, G. Raguin, A case-control study of risk factors for hepatitis C infection in patients with unexplained routes of infection, J. Viral. Hepat., 13 (2006) 775-782. |
| [12] | M. K. Mohamed, M. Abdel-Hamid, N. N. Mikhail, F. Abdel-Aziz, A. Medhat, L. S. Magder, A. D. Fix, G. T. Strickland, Intrafamilial transmission of hepatitis C in Egypt, Hepatol., 42 (2000) 683-687. |
| [13] | M. J. Alter, Epidemiology of hepatitis C virus infection, World J. Gastroenterol, 13 (2007) 2436-2441. |
| [14] | T. A. Steitz, DNA Polymerases: Structural Diversity and Common Mechanisms, J. Biol. Chem., 274 (1999) 17395–17398. |
| [15] | D. Das, J. Hong, S. Chen, G. Wang, L. Beigelman, S. D. Seiwert, B. O. Buckman, Recent advances in drug discovery of benzothiadiazine and related analogs as HCV NS5B polymerase inhibitors, Bioorg. Med. Chem., 19 (2011) 4690-4703. |
| [16] | L. Tomei, S. Altamura, G. Paonessa, R. De Francesco, G. Migliaccio, HCV antiviral resistance: the impact of in vitro studies on the development of antiviral agents targeting the viral NS5B polymerase, Antivir. Chem. Chemother., 16 (2005) 225–245. |
| [17] | S. Betzi, C. Eydouxc, C. Bussetta, M. Blemont, P. Leyssen, C. Debarnot, M. Ben-Rahou, J. Haiech, M. Hibert, F. Gueritte, D. S. Grierson, J.-L. Romette, J.-C. Guillemot, J. Neyts, K. Alvarez, X. Morelli, H. Dutartre, B. Canard, Identification of allosteric inhibitors blocking the hepatitis C virus polymerase NS5B in the RNA synthesis initiation step, Antiviral Res., 84 (2009) 48-59. |
| [18] | H. Li, J. Tatlock, A. Linton, J. Gonzalez, A. Borchardt, P. Dragovich, T. Jewell, T. Prins, R. Zhou, J. Blazel, H. Parge, R. Love, M. Hickey, C. Doan, S. Shi, R. Duggal, C. Lewis, S. Fuhrman, Identification and structure-based optimization of novel dihydropyrones as potent HCV RNA polymerase inhibitors, Bioorg. Med. Chem. Lett., 16 (2006) 4834–4838. |
| [19] | R. De Francesco, A. Carfí, 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. Deliv. Rev., 59 (2007) 1242–1262. |
| [20] | C. Vasquez, Allosteric effects of the GTP-specific binding site and a benzimidazole-derivative nonnucleoside inhibitor on the hepatitis C virus RNA-dependent RNA polymerase, Microbiology and Immunology, McGill University, Montreal, 2009. |
| [21] | U. Koch, F. Narjes, Allosteric Inhibition of the Hepatitis C Virus NS5B RNA Dependent RNA Polymerase, Infect. Disord. Drug. Targets., 6 (2006) 31-41. |
| [22] | S. Colarusso, B. Attenni, B. Attenni, S. Avolio, S. Malancona, S. Harper, S. Altamura, U. Koch, F. Narjes, Inhibitors of the hepatitis C virus RNA-dependent RNA polymerase, ARKIVOC vii (2006) 479-495. |
| [23] | M. H. Powdrill, J. A. Bernatchez, M. Götte, Inhibitors of the Hepatitis C Virus RNA-Dependent RNA Polymerase NS5B, Viruses 2(2010) 2169-2195. |
| [24] | J. Vermehren, C. Sarrazin, New HCV therapies on the horizon, Clin. Microbiol. Infect., 17 (2011) 122-134. D. B. Kitchen, H. Decornez, J. R. Furr, J. Bajorath, Docking and scoring in virtual screening for drug discovery: methods and applications, Nature reviews. Drug discovery, 3 (2004) 935–949. |
| [25] | C. Levinthal, S. Wodak, P. Kahn, A. Dadivanian, Hemoglobin interaction in sickle cell fibers. I: Theoretical approaches to the molecular contacts, Proc Natl Acad Sci 72 (1975) 1330–1334. |
| [26] | K. H. Kim, G. Greco, E. Novellino, A Critical Review of Recent CoMFA Applications 3D QSAR in Drug Design, in: H. Kubinyi, G. Folkers, Y. C. Martin (Eds.), Springer Netherlands2002, pp. 257-315. |
| [27] | H. Kubinyi, QSAR and 3D QSAR in drug design Part 1: methodology, Drug Discovery Today, 2 (1997) 457-467. |
| [28] | L. Zhang, K. C. Tsai, L. Du, H. Fang, M. Li, W. Xu, How to generate reliable and predictive CoMFA models, Curr. Med. Chem., 18 (2011) 923-930. |
| [29] | J. C. Shelley, A. Cholleti, L. Frye, J. R. Greenwood, M. R. Timlin, M. Uchimaya, Epik: a software program for pKa prediction and protonation state generation for drug-like molecules, J. Comp.-Aided Mol. Design, 21 (2007) 681-691. |
| [30] | A. E. Cho, D. Rinaldo, Extension of QM/MM docking and its applications to metalloproteins, J. Comput. Chem., 30 (2009) 2609-2616. |
| [31] | R. Farid, M. Ringnalda, M. Murcko, D. J. Weiser, Y. Tran, M. Byington, W. A. Glauser, S.-Y. Liu, A. Monge, S. Ozawa, L. Frye, W. Sherman, V. Eyrich, Y. Shimada, S. Becker, R. Abel, J. Vertrees, QM-Polarized Ligand Docking : A novel research solution that combines the power of Glide with the accuracy of QSite, in: R. Friesner, P. Anderson, B. J. Berne, W. C. Guida, B. Honig, M. P. Jacobson, W. L. Jorgensen, R. M. Levy (Eds.) Schrödinger is the scientific leader in computational chemistry, providing software solutions and services for life sciences and materials research, 2012. |
| [32] | R. Thomsen, M. H. Christensen, MolDock: A New Technique for High-Accuracy Molecular Docking, J. Med. Chem., 49 (2006) 3315-3321. |
| [33] | A. E. Cho, V. Guallar, B. Berne, R. A. Friesner, Importance of Accurate Charges in Molecular Docking: Quantum Mechanical/Molecular Mechanical (QM/MM) Approach, J. Comput. Chem., 26 (2005) 915-931. |
| [34] | A.-S. S. H. Elgazwy, N. S. M. Ismail, H. S. A. Elzahabi, 45 A convenient synthesis and molecular modeling study of novel purine and pyrimidine derivatives as CDK2/cyclin A3 inhibitors, Bioorg Med Chem, 18 (2010) 7639-7650. |
| [35] | M. ElHefnawi1, M. ElGamacy, M. Fares, Multiple virtual screening approaches for finding new Hepatitis c virus RNA-dependent RNA polymerase inhibitors: Structure-based screens and molecular dynamics for the pursue of new poly pharmacological inhibitors, BMC Bioinformatics 13 (2012) S5. |
| [36] | M. S. Bahia, S. K. Gunda, S. R. Gade, S. Mahmood, R. Muttineni, O. Silakari, Anthranilate derivatives as TACE inhibitors: docking based CoMFA and CoMSIA analyses, J Mol Model, 17 (2011) 9-19. |
| [37] | S. Boppana, N. S. Pagadala, K. S. Rangappa, structure based designing of new inhibitors a gainst acetylcholine esterase associated with Alzheimer's disease, in: K. S. Rangappa (Ed.) structure based designing of new inhibitors, 2009, pp. 29-36. |
| [38] | G. A. Balaji1, V. N. Balaji, S. N. Rao, Utility of scoring function customization in docking-based virtual screening approaches, Curr. Sci., 104 (2013). |
| [39] | V. Sobolev, A. Sorokine, J. Prilusky, E. E. Abola, M. Edelman, Automated analysis of interatomic contacts in proteins, Bioinformatics, 15 (1999) 327-332. |
| [40] | E. F. Pettersen, T. Goddard, C. Huang, G. S. Couch, D. M. Greenblatt, E. C. Meng, T. Ferrin, E., UCSF Chimera: a visualization system for exploratory research and analysis, J. Comput. Chem., 25 (2004) 1605-1612. |
| [41] | H. Abedi, H. Ebrahimzadeh, J. B. Ghasemi, 3D-QSAR, CoMFA, and CoMSIA of new phenyloxazolidinones derivatives as potent HIV-1 protease inhibitors, Structural Chemistry, 24 (2013) 433-444. |
| [42] | J. Gasteiger, M. Marsili, Iterative partial equalization of orbital electronegativity – a rapid access to atomic charges, Tetrahedron, 36 (1980) 3219–3228. |
| [43] | J. L. Medina-Franco, S. Rodríguez-Morales, C. Juárez-Gordiano, A. Hernández-Campos, R. Castillo, Docking-based CoMFA and CoMSIA studies of non-nucleoside reverse transcriptase inhibitors of the pyridinone derivative type, Journal of Computer-Aided Molecular Design, 18 (2004) 345-360. |
| [44] | C. Pargellis, L. Tong, L. Churchill, P. F. Cirillo, T. Gilmore, A. G. Graham, P. M. Grob, E. R. Hickey, N. Moss, S. Pav, J. Regan, Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site, Nat Struct Biol, 9 (2002) 268-272. |
| [45] | V. N. Viswanadhan, A. K. Ghose, G. R. Revankar, R. K. Robins, Atomic physicochemical parameters for three dimensional structure directed quantitative structure-activity relationships. 4. Additional parameters for hydrophobic and dispersive interactions and their application for an automated superposition of certain naturally occurring nucleoside antibiotics, Journal of Chemical Information and Computer Sciences, 29 (1989) 163-172. |
| [46] | S. Bressanelli, L. Tomei, F. A. Rey, R. De Francesco, Structural analysis of the hepatitis C virus RNA polymerase in complex with ribonucleotides, J. Virol., 76 (2002) 3482-3492. |
| [47] | A. E. Gorbalenya, F. M. Pringle, J. L. Zeddam, B. T. Luke, C. E. Cameron, J. Kalmakoff, T. N. Hanzlik, K. H. Gordon, V. K. Ward, The palm subdomain-based active site is internally permuted in viral RNA-dependent RNA polymerases of an ancient lineage, J. Mol. Biol., 324 (2002) 47–62. |
| [48] | E. K. O’Reilly, C. C. Kao, Analysis of RNA-dependent RNA polymerase structure and function as guided by known polymerase structures and computer predictions of secondary structure, Virology 252 (1998) 287–303. |
| [49] | C. A. Lesburg, R. Radfar, P. C. Weber, Recent advances in the analysis of HCV NS5B RNA-dependent RNA polymerase, Curr. Opin. Investig. Drugs., 1 (2000) 289-296. |
| [50] | C. A. Brautigam, T. A. Steitz, Structural and functional insights provided by crystal structures of DNA polymerases and their substrate complexes, Curr. Opin. Struct. Biol., 8 (1998) 54–63. |
| [51] | N. Ai-hua, Recent advances in HCV NS5B RNA-dependent RNA polymerase inhibitors, Journal of International Pharmaceutical Research, 39 (2012) 89-103. |
| [52] | T. Li, M. Froeyen, P. Herdewijn, Insight into ligand selectivity in HCV NS5B polymerase: molecular dynamics simulations, free energy decomposition and docking, J. Mol. Model., 16 (2010) 49-59. |
| [53] | D. Plewczynski, M. Łaźniewski, R. Augustyniak, K. Ginalski, Can we trust docking results? Evaluation of seven commonly used programs on PDBbind database, J. Comput. Chem., 32 (2011) 742-755. |
| [54] | R. A. Love, H. E. Parge, X. Yu, M. J. Hickey, W. Diehl, J. Gao, H. Wriggers, A. Ekker, L. Wang, J. A. Thomson, P. S. Dragovich, S. A. Fuhrman, Crystallographic identification of a noncompetitive inhibitor binding site on the hepatitis C virus NS5B RNA polymerase enzyme, J. Virol., 77 (2003) 7575-7581. |
| [55] | A. Arleo, A. Mangia, The current treatment of Hepatitis C, Minerva gastroenterologica e dietologica, 62 (2016) 167-182. |
| [56] | C. J. Monceaux, C. Hirata-Fukae, P. C. Lam, M. M. Totrov, Y. Matsuoka, P. R. Carlier, Triazole-linked reduced amide isosteres: an approach for the fragment-based drug discovery of anti-Alzheimer's BACE1 inhibitors, Bioorganic & medicinal chemistry letters, 21 (2011) 3992-3996. |
| [57] | S. Duhovny, D. Dror, O. Inbar, Y. Nussinov, R. Wolfson, J. Haim, PharmaGist: a webserver for ligand-based pharmacophore detection, Nucleic Acids Res., 36 (2008) W223-W228. |
| [58] | S. V. Damme, Quantum chemistry in QSAR : Quantum chemical descriptors :Use, benefits and drawbacks, Department of Inorganic and Physical Chemistry, Ghent University, Ghent, 2009, pp. 349. |
APA Style
Yasmine Shafike Moemen, Ahmed Mahmoud El-Nahas, Ahmed Helmy Ebraheem Hassan, Safwat Abdel-Azeim, Serry Atta Atta El-Bialy. (2017). Docking and 3D-QSAR Studies on Some HCV NS5b Inhibitors. Journal of Drug Design and Medicinal Chemistry, 3(4), 49-59. https://doi.org/10.11648/j.jddmc.20170304.11
ACS Style
Yasmine Shafike Moemen; Ahmed Mahmoud El-Nahas; Ahmed Helmy Ebraheem Hassan; Safwat Abdel-Azeim; Serry Atta Atta El-Bialy. Docking and 3D-QSAR Studies on Some HCV NS5b Inhibitors. J. Drug Des. Med. Chem. 2017, 3(4), 49-59. doi: 10.11648/j.jddmc.20170304.11
AMA Style
Yasmine Shafike Moemen, Ahmed Mahmoud El-Nahas, Ahmed Helmy Ebraheem Hassan, Safwat Abdel-Azeim, Serry Atta Atta El-Bialy. Docking and 3D-QSAR Studies on Some HCV NS5b Inhibitors. J Drug Des Med Chem. 2017;3(4):49-59. doi: 10.11648/j.jddmc.20170304.11
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Download@article{10.11648/j.jddmc.20170304.11,
author = {Yasmine Shafike Moemen and Ahmed Mahmoud El-Nahas and Ahmed Helmy Ebraheem Hassan and Safwat Abdel-Azeim and Serry Atta Atta El-Bialy},
title = {Docking and 3D-QSAR Studies on Some HCV NS5b Inhibitors},
journal = {Journal of Drug Design and Medicinal Chemistry},
volume = {3},
number = {4},
pages = {49-59},
doi = {10.11648/j.jddmc.20170304.11},
url = {https://doi.org/10.11648/j.jddmc.20170304.11},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jddmc.20170304.11},
abstract = {A theoretical study has been carried out to interpret and support experimental findings regarding inhibition mechanism of HCV NS5b. Twenty-five HCV NS5b inhibitors were docked by QM-Polarized Ligand Docking (QPLD) technique. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods were used to derive 3D-QSAR models for the selected inhibitors. The CoMFA and CoMSIA models show good cross-validated (Q2) and non-cross-validated (R2) coefficients for the suggested inhibitors of 0.43, 0.98 and 0.65, 0.99, respectively. The inhibition mechanism was explored and validated. Details of the interactions between the inhibitors and HCV NS5b are given in terms of steric, electrostatic, hydrophobic, hydrogen bonding fields. Enhancing potency via substitutions at positions, which were explored based on these parameters. A good correlation was found between 3D-QSAR and docking results.},
year = {2017}
}
TY - JOUR T1 - Docking and 3D-QSAR Studies on Some HCV NS5b Inhibitors AU - Yasmine Shafike Moemen AU - Ahmed Mahmoud El-Nahas AU - Ahmed Helmy Ebraheem Hassan AU - Safwat Abdel-Azeim AU - Serry Atta Atta El-Bialy Y1 - 2017/10/23 PY - 2017 N1 - https://doi.org/10.11648/j.jddmc.20170304.11 DO - 10.11648/j.jddmc.20170304.11 T2 - Journal of Drug Design and Medicinal Chemistry JF - Journal of Drug Design and Medicinal Chemistry JO - Journal of Drug Design and Medicinal Chemistry SP - 49 EP - 59 PB - Science Publishing Group SN - 2472-3576 UR - https://doi.org/10.11648/j.jddmc.20170304.11 AB - A theoretical study has been carried out to interpret and support experimental findings regarding inhibition mechanism of HCV NS5b. Twenty-five HCV NS5b inhibitors were docked by QM-Polarized Ligand Docking (QPLD) technique. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods were used to derive 3D-QSAR models for the selected inhibitors. The CoMFA and CoMSIA models show good cross-validated (Q2) and non-cross-validated (R2) coefficients for the suggested inhibitors of 0.43, 0.98 and 0.65, 0.99, respectively. The inhibition mechanism was explored and validated. Details of the interactions between the inhibitors and HCV NS5b are given in terms of steric, electrostatic, hydrophobic, hydrogen bonding fields. Enhancing potency via substitutions at positions, which were explored based on these parameters. A good correlation was found between 3D-QSAR and docking results. VL - 3 IS - 4 ER -
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