Multiple e-pharmacophore modeling, 3D-QSAR, and high-throughput virtual screening of hepatitis C virus NS5B polymerase inhibitors

Journal of Chemical Information and Modeling

Volumn 54, Issue 2, 2014, Pages 539-552

  Therese, Patrisha Joseph ^a   Manvar, Dinesh ^b   Kondepudi, Sridevi ^a   Battu, Madhu Babu ^a   Sriram, Dharmarajan ^a   Basu, Amartya ^b   Yogeeswari, Perumal ^a   Kaushik Basu, Neerja ^b,c  

^a BIRLA INSTITUTE OF TECHNOLOGY AND SCIENCE   (India)

^b RUTGERS NEW JERSEY MEDICAL SCHOOL   (United States)

^c RUTGERS CANCER INSTITUTE OF NEW JERSEY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3D MODELING; COMPUTATIONAL CHEMISTRY; CRYSTALS; MACHINERY; PHARMACODYNAMICS; POLYMERS; RNA; SCAFFOLDS (BIOLOGY); VIRUSES;

HEPATITIS C VIRUS; HEPATITIS C VIRUS NS5B POLYMERASE; INHIBITOR COMPLEX; MOLECULAR DOCKING; PHARMACOPHORE MODELING; PHARMACOPHORE MODELS; RNA-DEPENDENT RNA POLYMERASE; VIRTUAL SCREENING;

VIRTUAL REALITY;

ANTIVIRUS AGENT; ENZYME INHIBITOR; NS 5 PROTEIN, HEPATITIS C VIRUS; NS-5 PROTEIN, HEPATITIS C VIRUS; VIRUS PROTEIN;

ARTICLE; CELL LINE; CHEMISTRY; COMPUTER INTERFACE; DRUG ANTAGONISM; DRUG EFFECT; DRUG SCREENING; ENZYMOLOGY; HEPATITIS C VIRUS; HIGH THROUGHPUT SCREENING; HUMAN; METABOLISM; MOLECULAR DOCKING; PROTEIN CONFORMATION; QUANTITATIVE STRUCTURE ACTIVITY RELATION; THERMODYNAMICS;

ANTIVIRAL AGENTS; CELL LINE; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; HEPACIVIRUS; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; MOLECULAR DOCKING SIMULATION; PROTEIN CONFORMATION; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; THERMODYNAMICS; USER-COMPUTER INTERFACE; VIRAL NONSTRUCTURAL PROTEINS;

EID: 84894679841     PISSN: 15499596     EISSN: 1549960X     Source Type: Journal    
DOI: 10.1021/ci400644r     Document Type: Article

References (38)

1. WHO. HepatitisC. Fact sheet no. 164, (2011; accessed at www.who.int/mediacenter/factsheet/fs164/en/.
2. Manns, M. P.; Foster, G. R.; Rockstroh, J. K.; Zeuzem, S.; Zoulim, F.; Houghton, M. The way forward in HCV treatment - finding the right path Nat. Rev. Drug Discovery 2007, 6, 991-1000
3. Sarrazin, C.; Zeuzem, S. Resistance to direct antiviral agents in patients with hepatitis C virus infection Gastroenterology 2010, 138, 447-62
4. Behrens, S. E.; Tomei, L.; De Francesco, R. Identification and properties of the RNA-dependent RNA polymerase of hepatitis C virus EMBO J. 1996, 15, 12-22
5. Moradpour, D.; Brass, V.; Bieck, E.; Friebe, P.; Gosert, R.; Blum, H. E.; Bartenschlager, R.; Penin, F.; Lohmann, V. Membrane association of the RNA-dependent RNA polymerase is essential for hepatitis C virus RNA replication J. Virol. 2004, 78, 13278-84
6. Rice, C. Perspective: miles to go before we sleep Nature 2011, 474, S8
7. Hagedorn, C. H.; van Beers, E. H.; De Staercke, C. Hepatitis C virus RNA-dependent RNA polymerase (NS5B polymerase) Curr. Top. Microbiol. Immunol. 2000, 242, 225-60
8. Tomei, L.; Vitale, R. L.; Incitti, I.; Serafini, S.; Altamura, S.; Vitelli, A.; De Francesco, R. Biochemical characterization of a hepatitis C virus RNA-dependent RNA polymerase mutant lacking the C-terminal hydrophobic sequence J. Gen. Virol. 2000, 81, 759-67
9. Lesburg, C. A.; Cable, M. B.; Ferrari, E.; Hong, Z.; Mannarino, A. F.; Weber, P. C. Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site Nat. Struct. Biol. 1999, 6, 937-43
10. Ruebsam, F.; Sun, Z.; Ayida, B. K.; Webber, S. E.; Zhou, Y.; Zhao, Q.; Kissinger, C. R.; Showalter, R. E.; Shah, A. M.; Tsan, M.; Patel, R.; Lebrun, L. A.; Kamran, R.; Sergeeva, M. V.; Bartkowski, D. M.; Nolan, T. G.; Norris, D. A.; Kirkovsky, L. Hexahydro-pyrrolo- and hexahydro-1H-pyrido[1,2-b]pyridazin-2- ones as potent inhibitors of HCV NS5B polymerase Bioorg. Med. Chem. Lett. 2008, 18, 5002-5
11. Ruebsam, F.; Webber, S. E.; Tran, M. T.; Tran, C. V.; Murphy, D. E.; Zhao, J.; Dragovich, P. S.; Kim, S. H.; Li, L. S.; Zhou, Y.; Han, Q.; Kissinger, C. R.; Showalter, R. E.; Lardy, M.; Shah, A. M.; Tsan, M.; Patel, R.; Lebrun, L. A.; Kamran, R.; Sergeeva, M. V.; Bartkowski, D. M.; Nolan, T. G.; Norris, D. A.; Kirkovsky, L. Pyrrolo[1,2-b]pyridazin-2-ones as potent inhibitors of HCV NS5B polymerase Bioorg. Med. Chem. Lett. 2008, 18, 3616-21
12. Maynard, A.; Crosby, R. M.; Ellis, B.; Hamatake, R.; Hong, Z.; Johns, B. A.; Kahler, K. M.; Koble, C.; Leivers, A. L.; Leivers, M. R.; Mathis, A.; Peat, A. J.; Pouliot, J. J.; Roberts, C. D.; Samano, V.; Schmidt, R. M.; Smith, G. K.; Spaltenstein, A.; Stewart, E. L.; Thommes, P.; Turner, E. M.; Voitenleitner, C.; Walker, J. T.; Waitt, G.; Weatherhead, J.; Weaver, K. L.; Williams, S.; Wright, L.; Xiong, Z. Z.; Haigh, D.; Shotwell, J. B. Discovery of a potent boronic acid derived inhibitor of the HCV RNA-dependent RNA polymerase J. Med. Chem. 2013, 10.1021/jm400317w
13. Biswal, B. K.; Wang, M.; Cherney, M. M.; Chan, L.; Yannopoulos, C. G.; Bilimoria, D.; Bedard, J.; James, M. N. Non-nucleoside inhibitors binding to hepatitis C virus NS5B polymerase reveal a novel mechanism of inhibition J. Mol. Biol. 2006, 361, 33-45
14. Bressanelli, S.; Tomei, L.; Rey, F. A.; De Francesco, R. Structural analysis of the hepatitis C virus RNA polymerase in complex with ribonucleotides J. Virol. 2002, 76, 3482-92
15. Bressanelli, S.; Tomei, L.; Roussel, A.; Incitti, I.; Vitale, R. L.; Mathieu, M.; De Francesco, R.; Rey, F. A. Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 13034-9
16. Patil, V. M.; Gupta, S. P.; Samanta, S.; Masand, N. Current perspective of HCV NS5B inhibitors: a review Curr. Med. Chem. 2011, 18, 5564-97
17. Yan, S.; Appleby, T.; Larson, G.; Wu, J. Z.; Hamatake, R. K.; Hong, Z.; Yao, N. Thiazolone-acylsulfonamides as novel HCV NS5B polymerase allosteric inhibitors: convergence of structure-based drug design and X-ray crystallographic study Bioorg. Med. Chem. Lett. 2007, 17, 1991-5
18. Schoenfeld, R. C.; Bourdet, D. L.; Brameld, K. A.; Chin, E.; de Vicente, J.; Fung, A.; Harris, S. F.; Lee, E. K.; Le Pogam, S.; Leveque, V.; Li, J.; Lui, A. S.; Najera, I.; Rajyaguru, S.; Sangi, M.; Steiner, S.; Talamas, F. X.; Taygerly, J. P.; Zhao, J. Discovery of a novel series of potent non-nucleoside inhibitors of Hepatitis C virus NS5B J. Med. Chem. 2013, 56, 8163-82
19. Hucke, O.; Coulombe, R.; Bonneau, P.; Bertrand-Laperle, M.; Brochu, C.; Gillard, J.; Joly, M. A.; Landry, S.; Lepage, O.; Llinas-Brunet, M.; Pesant, M.; Poirier, M.; Poirier, M.; McKercher, G.; Marquis, M.; Kukolj, G.; Beaulieu, P. L.; Stammers, T. A. Molecular dynamics simulations and structure-based rational design lead to allosteric HCV NS5B polymerase thumb pocket 2 inhibitor with picomolar cellular replicon potency J. Med. Chem. 2013, 10.1021/jm4004522
20. Beaulieu, P. L.; Coulombe, R.; Duan, J.; Fazal, G.; Godbout, C.; Hucke, O.; Jakalian, A.; Joly, M. A.; Lepage, O.; Llinas-Brunet, M.; Naud, J.; Poirier, M.; Rioux, N.; Thavonekham, B.; Kukolj, G.; Stammers, T. A. Structure-based design of novel HCV NS5B thumb pocket 2 allosteric inhibitors with submicromolar gt1 replicon potency: discovery of a quinazolinone chemotype Bioorg. Med. Chem. Lett. 2013, 23, 4132-40
21. Yu, H.; Fang, Y.; Lu, X.; Liu, Y.; Zhang, H. 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. 2013, 10.1111/cbdd.12203
22. Zhang, H. X.; Li, Y.; Wang, X.; Xiao, Z. T.; Wang, Y. H. Insight into the structural requirements of benzothiadiazine scaffold-based derivatives as hepatitis C virus NS5B polymerase inhibitors using 3D-QSAR, molecular docking and molecular dynamics Curr. Med. Chem. 2011, 18, 4019-28
23. Wang, X.; Yang, W.; Xu, X.; Zhang, H.; Li, Y.; Wang, Y. Studies of benzothiadiazine derivatives as hepatitis C virus NS5B polymerase inhibitors using 3D-QSAR, molecular docking and molecular dynamics Curr. Med. Chem. 2010, 17, 2788-803
24. Musmuca, I.; Caroli, A.; Mai, A.; Kaushik-Basu, N.; Arora, P.; Ragno, R. Combining 3-D quantitative structure-activity relationship with ligand based and structure based alignment procedures for in silico screening of new hepatitis C virus NS5B polymerase inhibitors J. Chem. Inf. Model. 2010, 50, 662-76
25. Palakurti, R.; Sriram, D.; Yogeeswari, P.; Vadrevu, R. Multiple e-pharmacophore modeling combined with high-throughput virtual screening and docking to identify potential inhibitors of β-secretase (BACE1) Mol. Inf. 2013, 32, 385-398
26. Dixon, S. L.; Smondyrev, A. M.; Knoll, E. H.; Rao, S. N.; Shaw, D. E.; Friesner, R. A. PHASE: a new engine for pharmacophore perception, 3D-QSAR model development, and 3D database screening: 1. Methodology and preliminary results J. Comput.-Aided Mol. Des. 2006, 20, 647-71
27. Lewis, R. A. A general method for exploiting QSAR models in lead optimization J. Med. Chem. 2005, 48, 1638-48
28. Consonni, V.; Ballabio, D.; Todeschini, R. Comments on the definition of the Q2 parameter for QSAR validation J.Chem. Inf. Model. 2009, 49, 1669-78
29. Halgren, T. A.; Murphy, R. B.; Friesner, R. A.; Beard, H. S.; Frye, L. L.; Pollard, W. T.; Banks, J. L. Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening J. Med. Chem. 2004, 47, 1750-9
30. Loving, K.; Salam, N. K.; Sherman, W. Energetic analysis of fragment docking and application to structure-based pharmacophore hypothesis generation J. Comput.-Aided Mol. Des. 2009, 23, 541-54
31. Truchon, J. F.; Bayly, C. I. Evaluating virtual screening methods: good and bad metrics for the "early recognition" problem J. Chem. Inf. Model. 2007, 47, 488-508
32. Pratim Roy, P.; Paul, S.; Mitra, I.; Roy, K. On two novel parameters for validation of predictive QSAR models Molecules 2009, 14, 1660-701
33. Battu, M. B.; Chandra, A. M.; Sriram, D.; Yogeeswari, P. Pharmacophore-based 3D-QSAR and molecular docking studies to identify new non-peptidic inhibitors of cathepsin S Curr. Med. Chem. 2013, Sep, 24059223
34. Kim, K.; Kim, K. H.; Kim, H. Y.; Cho, H. K.; Sakamoto, N.; Cheong, J. Curcumin inhibits hepatitis C virus replication via suppressing the Akt-SREBP-1 pathway FEBS Lett. 2010, 584, 707-712
35. Nichols, D. B.; Fournet, G.; Gurukumar, K. R.; Basu, A.; Lee, J. C.; Sakamoto, N.; Kozielski, F.; Musmuca, I.; Joseph, B.; Ragno, R.; Kaushik-Basu, N. Inhibition of hepatitis C virus NS5B polymerase by S-trityl-L-cysteine derivatives Eur. J. Med. Chem. 2012, 49, 191-9
36. Kaushik-Basu, N.; Bopda-Waffo, A.; Talele, T. T.; Basu, A.; Costa, P. R.; da Silva, A. J.; Sarafianos, S. G.; Noel, F. Identification and characterization of coumestans as novel HCV NS5B polymerase inhibitors Nucleic Acids Res. 2008, 36, 1482-96
37. Chen, Y.; Bopda-Waffo, A.; Basu, A.; Krishnan, R.; Silberstein, E.; Taylor, D. R.; Talele, T. T.; Arora, P.; Kaushik-Basu, N. Characterization of aurintricarboxylic acid as a potent hepatitis C virus replicase inhibitor Antiviral Chem. Chemother. 2009, 20, 19-36
38. Svetnik, V.; Liaw, A.; Tong, C.; Culberson, J. C.; Sheridan, R. P.; Feuston, B. P. Random forest: a classification and regression tool for compound classification and QSAR modeling J. Chem. Inf. Comput. Sci. 2003, 43, 1947-58