QSAR studies on hepatitis C virus NS5A protein tetracyclic inhibitors in wild type and mutants by CoMFA and CoMSIA

References

• World health organization, hepatitis C page. Available at https://www.who.int/en/news-room/fact-sheets/detail/hepatitis-c (accessed Feb, 2020).
   Google Scholar
• A. Grakoui, D.W. McCourt, C. Wychowski, S.M. Feinstone, and C.M. Rice, Characterization of the hepatitis C virus-encoded serine proteinase: Determination of proteinase-dependent polyprotein cleavage sites, J. Virol. 67 (1993), pp. 2832–2843. doi:10.1128/JVI.67.5.2832-2843.1993.
   PubMed Web of Science ®Google Scholar
• C. Sheridan, New Merck and Vertex drugs raise standard of care in hepatitis C, Nat. Biotechnol. 29 (2011), pp. 553–554. doi:10.1038/nbt0711-553.
   PubMed Web of Science ®Google Scholar
• T.K.H. Scheel and C.M. Rice, Understanding the hepatitis C virus life cycle paves the way for highly effective therapies, Nat. Med. 19 (2013), pp. 837–849. doi:10.1038/nm.3248.
   PubMed Web of Science ®Google Scholar
• T.L. Tellinghuisen, J. Marcotrigiano, and C.M. Rice, Structure of the zinc-binding domain of an essential component of the hepatitis C virus replicase, Nature 435 (2005), pp. 374–379. doi:10.1038/nature03580.
   PubMed Web of Science ®Google Scholar
• R.A. Love, O. Brodsky, M.J. Hickey, P.A. Wells, and C.N. Cronin, Crystal structure of a novel dimeric form of NS5A domain i protein from hepatitis C virus, J. Virol. 83 (2009), pp. 4395–4403. doi:10.1128/JVI.02352-08.
   PubMed Web of Science ®Google Scholar
• S.M. Lambert, D.R. Langley, J.A. Garnett, R. Angell, K. Richard, N.A. Meanwell, and S.J. Matthews, The crystal structure of NS5A domain 1 from genotype 1a reveals new clues to the mechanism of action for dimeric HCV inhibitors, Protein Sci. 23 (2014), pp. 723–734. doi:10.1002/pro.2456.
   PubMed Web of Science ®Google Scholar
• K.H. Barakat, A. Anwar-Mohamed, J.A. Tuszynski, M.J. Robins, D.L. Tyrrell, and M. Houghton, A refined model of the HCV NS5A protein bound to daclatasvir explains drug-resistant mutations and activity against divergent genotypes, J. Chem. Inf. Model. 55 (2015), pp. 362–373. doi:10.1021/ci400631n.
   PubMed Web of Science ®Google Scholar
• M. Ahmed, A. Pal, M. Houghton, and K. Barakat, A comprehensive computational analysis for the binding modes of hepatitis C virus NS5A inhibitors: The question of symmetry, ACS Infect. Dis. 2 (2016), pp. 872–881. doi:10.1021/acsinfecdis.6b00113.
   PubMed Web of Science ®Google Scholar
• M. Gao, R.E. Nettles, M. Belema, L.B. Snyder, V.N. Nguyen, R.A. Fridell, M.H. Serrano-Wu, D.R. Langley, J.-H. Sun, D.R. O’Boyle II, J.A. Lemm, C. Wang, J.O. Knipe, C. Chien, R.J. Colonno, D.M. Grasela, N.A. Meanwell, and L.G. Hamann, Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect, Nature 465 (2010), pp. 96–100. doi:10.1038/nature08960.
   PubMed Web of Science ®Google Scholar
• M. Belema and N.A. Meanwell, Discovery of daclatasvir, a pan-genotypic hepatitis C virus NS5A replication complex inhibitor with potent clinical effect, J. Med. Chem. 57 (2014), pp. 5057–5071. doi:10.1021/jm500335h.
   PubMed Web of Science ®Google Scholar
• J.O. Link, J.G. Taylor, L. Xu, M. Mitchell, H. Guo, H. Liu, D. Kato, T. Kirschberg, J. Sun, N. Squires, J. Parrish, T. Keller, Z.Y. Yang, C. Yang, M. Matles, Y. Wang, K. Wang, G. Cheng, Y. Tian, E. Mogalian, E. Mondou, M. Cornpropst, J. Perry, and M.C. Desai, Discovery of ledipasvir (GS-5885): A potent, once-daily oral NS5A inhibitor for the treatment of hepatitis C virus infection, J. Med. Chem. 57 (2014), pp. 2033–2046. doi:10.1021/jm401499g.
   PubMed Web of Science ®Google Scholar
• C.A. Coburn, P.T. Meinke, W. Chang, C.M. Fandozzi, D.J. Graham, B. Hu, Q. Huang, S. Kargman, J. Kozlowski, R. Liu, J.A. McCauley, A.A. Nomeir, R.M. Soll, J.P. Vacca, D. Wang, H. Wu, B. Zhong, D.B. Olsen, and S.W. Ludmerer, Discovery of MK-8742: An HCV NS5A inhibitor with broad genotype activity, ChemMedChem 8 (2013), pp. 1930–1940. doi:10.1002/cmdc.201300343.
   PubMed Web of Science ®Google Scholar
• E.J. Lawitz, H. Dvory-Sobol, B.P. Doehle, A.S. Worth, J. McNally, D.M. Brainard, J.O. Link, M.D. Miller, and H. Mo, Clinical resistance to velpatasvir (GS-5816), a novel pan-genotypic inhibitor of the hepatitis C virus NS5A protein, Antimicrob. Agents Chemother. 60 (2016), pp. 5368–5378. doi:10.1128/AAC.00763-16.
   PubMed Web of Science ®Google Scholar
• D.A. Degoey, J.T. Randolph, D. Liu, J. Pratt, C. Hutchins, P. Donner, A.C. Krueger, M. Matulenko, S. Patel, C.E. Motter, L. Nelson, R. Keddy, M. Tufano, D.D. Caspi, P. Krishnan, N. Mistry, G. Koev, T.J. Reisch, R. Mondal, T. Pilot-Matias, Y. Gao, D.W.A.A. Beno, C.J. Maring, A. Molla, E. Dumas, A. Campbell, L. Williams, C. Collins, R. Wagner, and W.M. Kati, Discovery of ABT-267, a pan-genotypic inhibitor of HCV NS5A, J. Med. Chem. 57 (2014), pp. 2047–2057. doi:10.1021/jm401398x.
   PubMed Web of Science ®Google Scholar
• T.I. Ng, P. Krishnan, T. Pilot-Matias, W. Kati, G. Schnell, J. Beyer, T. Reisch, L. Lu, T. Dekhtyar, M. Irvin, R. Tripathi, C. Maring, J.T. Randolph, R. Wagner, and C. Collins, In vitro antiviral activity and resistance profile of the next-generation hepatitis C virus NS5A inhibitor pibrentasvir, Antimicrob. Agents Chemother. 61 (2017), pp. e02558–16. doi:10.1128/AAC.02558-16.
   PubMed Web of Science ®Google Scholar
• R. Wagner, J.T. Randolph, S.V. Patel, L. Nelson, M.A. Matulenko, R. Keddy, J.K. Pratt, D. Liu, A.C. Krueger, P.L. Donner, D.K. Hutchinson, C. Flentge, D. Betebenner, T. Rockway, C.J. Maring, T.I. Ng, P. Krishnan, T. Pilot-Matias, C. Collins, N. Panchal, T. Reisch, T. Dekhtyar, R. Mondal, D.F. Stolarik, Y. Gao, W. Gao, D.A. Beno, and W.M. Kati, Highlights of the structure–activity relationships of benzimidazole linked pyrrolidines leading to the discovery of the hepatitis C virus NS5A inhibitor pibrentasvir (ABT-530), J. Med. Chem. 61 (2018), pp. 4052–4066. doi:10.1021/acs.jmedchem.8b00082.
   PubMed Web of Science ®Google Scholar
• D.B. Smith, J. Bukh, C. Kuiken, A.S. Muerhoff, C.M. Rice, J.T. Stapleton, and P. Simmonds, Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: Updated criteria and genotype assignment web resource, Hepatology 59 (2014), pp. 318–327. doi:10.1002/hep.26744.
   PubMed Web of Science ®Google Scholar
• W. Yu, C.A. Coburn, A.G. Nair, M. Wong, S.B. Rosenblum, G. Zhou, M.P. Dwyer, L. Tong, B. Hu, B. Zhong, J. Hao, T. Ji, S. Zan, S.H. Kim, Q. Zeng, O. Selyutin, L. Chen, F. Masse, S. Agrawal, R. Liu, E. Xia, Y. Zhai, S. Curry, P. McMonagle, P. Ingravallo, E. Asante-Appiah, M. Lin, and J.A. Kozlowski, Aryl or heteroaryl substituted aminal derivatives of HCV NS5A inhibitor MK-8742, Bioorg. Med. Chem. Lett. 26 (2016), pp. 3414–3420. doi:10.1016/j.bmcl.2016.06.056.
   PubMed Web of Science ®Google Scholar
• W. Yu, C.A. Coburn, A.G. Nair, M. Wong, L. Tong, M.P. Dwyer, B. Hu, B. Zhong, J. Hao, D.Y. Yang, O. Selyutin, Y. Jiang, S.B. Rosenblum, S.H. Kim, B.J. Lavey, G. Zhou, R. Rizvi, B.B. Shankar, Q. Zeng, L. Chen, S. Agrawal, D. Carr, L. Rokosz, R. Liu, S. Curry, P. McMonagle, P. Ingravallo, F. Lahser, E. Asante-Appiah, A. Nomeir, and J.A. Kozlowski, Alkyl substituted aminal derivatives of HCV NS5A inhibitor MK-8742, Bioorg. Med. Chem. Lett. 26 (2016), pp. 3800–3805. doi:10.1016/j.bmcl.2016.05.041.
   PubMed Web of Science ®Google Scholar
• A.G. Nair, Q. Zeng, O. Selyutin, S.B. Rosenblum, Y. Jiang, D.-Y. Yang, K. Keertikar, G. Zhou, M. Dwyer, S.H. Kim, B. Shankar, W. Yu, L. Tong, L. Chen, R. Mazzola, J. Caldwell, H. Tang, S. Agrawal, R. Liu, R. Kong, P. Ingravallo, E. Xia, Y. Zhai, A. Nomeir, E. Asante-Appiah, and J.A. Kozlowski, MK-8325: A silyl proline-containing NS5A inhibitor with pan-genotype activity for treatment of HCV, Bioorg. Med. Chem. Lett. 28 (2018), pp. 1954–1957. doi:10.1016/j.bmcl.2018.03.049.
   PubMed Web of Science ®Google Scholar
• W. Yu, L. Tong, B. Hu, B. Zhong, J. Hao, T. Ji, S. Zan, C.A. Coburn, O. Selyutin, L. Chen, L. Rokosz, S. Agrawal, R. Liu, S. Curry, P. McMonagle, P. Ingravallo, E. Asante-Appiah, S. Chen, and J.A. Kozlowski, Discovery of chromane containing hepatitis C virus (HCV) NS5A inhibitors with improved potency against resistance-associated variants, J. Med. Chem. 59 (2016), pp. 10228–10243. doi:10.1021/acs.jmedchem.6b01234.
   PubMed Web of Science ®Google Scholar
• L. Tong, W. Yu, L. Chen, O. Selyutin, M.P. Dwyer, A.G. Nair, R. Mazzola, J.-H. Kim, D. Sha, J. Yin, R.T. Ruck, I.W. Davies, B. Hu, B. Zhong, J. Hao, T. Ji, S. Zan, R. Liu, S. Agrawal, E. Xia, S. Curry, P. McMonagle, K. Bystol, F. Lahser, D. Carr, L. Rokosz, P. Ingravallo, S. Chen, K.-I. Feng, M. Cartwright, E. Asante-Appiah, and J.A. Kozlowski, Discovery of ruzasvir (MK-8408): A potent, pan-genotype HCV NS5A inhibitor with optimized activity against common resistance-associated polymorphisms, J. Med. Chem. 60 (2017), pp. 290–306. doi:10.1021/acs.jmedchem.6b01310.
   PubMed Web of Science ®Google Scholar
• W. Yu, L. Tong, O. Selyutin, L. Chen, B. Hu, B. Zhong, J. Hao, T. Ji, S. Zan, J. Yin, R.T. Ruck, S. Curry, P. McMonagle, S. Agrawal, L. Rokosz, D. Carr, P. Ingravallo, K. Bystol, F. Lahser, R. Liu, S. Chen, K.-I. Feng, M. Cartwright, E. Asante-Appiah, and J.A. Kozlowski, Discovery of MK-6169, a potent pan-genotype hepatitis C virus NS5A inhibitor with optimized activity against common resistance-associated substitutions, J. Med. Chem. 61 (2018), pp. 3984–4003. doi:10.1021/acs.jmedchem.7b01927.
   PubMed Web of Science ®Google Scholar
• A. Cherkasov, E.N. Muratov, D. Fourches, A. Varnek, I.I. Baskin, M. Cronin, J. Dearden, P. Gramatica, Y.C. Martin, R. Todeschini, V. Consonni, V.E. Kuz’Min, R. Cramer, R. Benigni, C. Yang, J. Rathman, L. Terfloth, J. Gasteiger, A. Richard, and A. Tropsha, QSAR modeling: Where have you been? Where are you going to? J. Med. Chem. 57 (2014), pp. 4977–5010. doi:10.1021/jm4004285.
   PubMed Web of Science ®Google Scholar
• J. Li, W. Tian, D. Gao, Y. Li, Y. Chang, J. Xu, J. Zheng, and P. Sun, QSAR studies on thiazole derivatives as HCV NS5A inhibitors via CoMFA and CoMSIA methods, Lett. Drug Des. Discov. 16 (2019), pp. 453–460. doi:10.2174/1570180815666180702153529.
   Web of Science ®Google Scholar
• L. Tong, W. Yu, C.A. Coburn, L. Chen, O. Selyutin, Q. Zeng, M.P. Dwyer, A.G. Nair, B.B. Shankar, S.H. Kim, D.Y. Yang, S.B. Rosenblum, R.T. Ruck, I.W. Davies, B. Hu, B. Zhong, J. Hao, T. Ji, S. Zan, R. Liu, S. Agrawal, D. Carr, S. Curry, P. McMonagle, K. Bystol, F. Lahser, P. Ingravallo, S. Chen, E. Asante-Appiah, and J.A. Kozlowski, Structure–activity relationships of proline modifications around the tetracyclic-indole class of NS5A inhibitors, Bioorg. Med. Chem. Lett. 26 (2016), pp. 5354–5360. doi:10.1016/j.bmcl.2016.08.097.
   PubMed Web of Science ®Google Scholar
• W. Yu, G. Zhou, C.A. Coburn, Q. Zeng, L. Tong, M.P. Dwyer, B. Hu, B. Zhong, J. Hao, T. Ji, S. Zan, L. Chen, R. Mazzola, J.H. Kim, D. Sha, O. Selyutin, S.B. Rosenblum, B. Lavey, A.G. Nair, S. Heon Kim, K.M. Keertikar, L. Rokosz, S. Agrawal, R. Liu, E. Xia, Y. Zhai, S. Curry, P. McMonagle, P. Ingravallo, E. Asante-Appiah, S. Chen, and J.A. Kozlowski, Substituted tetracyclic indole core derivatives of HCV NS5A inhibitor MK-8742, Bioorg. Med. Chem. Lett. 26 (2016), pp. 4851–4856. doi:10.1016/j.bmcl.2016.08.002.
   PubMed Web of Science ®Google Scholar
• M.P. Dwyer, K.M. Keertikar, L. Chen, L. Tong, O. Selyutin, A.G. Nair, W. Yu, G. Zhou, B.J. Lavey, D.Y. Yang, M. Wong, S.H. Kim, C.A. Coburn, S.B. Rosenblum, Q. Zeng, Y. Jiang, B.B. Shankar, R. Rizvi, A.A. Nomeir, R. Liu, S. Agrawal, E. Xia, R. Kong, Y. Zhai, P. Ingravallo, E. Asante-Appiah, and J.A. Kozlowski, Matched and mixed cap derivatives in the tetracyclic indole class of HCV NS5A inhibitors, Bioorg. Med. Chem. Lett. 26 (2016), pp. 4106–4111. doi:10.1016/j.bmcl.2016.06.063.
   PubMed Web of Science ®Google Scholar
• D. Rogers and M. Hahn, Extended-connectivity fingerprints, J. Chem. Inf. Model. 50 (2010), pp. 742–754. doi:10.1021/ci100050t.
   PubMed Web of Science ®Google Scholar
• RDKit 2019.03.1. An open-source cheminformatics software, San Francisco, CA, USA, 2019; Available at http://www.rdkit.org (accessed Feb, 2020).
   Google Scholar
• F. Pedregosa, G. Varoquaux, A. Gramfort, V. Michel, B. Thirion, O. Grisel, M. Blondel, P. Prettenhofer, R. Weiss, V. Dubourg, J. Vanderplas, A. Passos, D. Cournapeau, M. Brucher, M. Perrot, and É. Duchesnay, Scikit-learn: Machine learning in Python, J. Mach. Learn. Res. 12 (2011), pp. 2825–2830.
   Web of Science ®Google Scholar
• NumPy. A fundamental package for scientific computing with Python; Available at https://numpy.org (accessed Feb, 2020).
   Google Scholar
• R.D. Cramer, D.E. Patterson, and J.D. Bunce, Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins, J. Am. Chem. Soc. 110 (1988), pp. 5959–5967. doi:10.1021/ja00226a005.
   PubMed Web of Science ®Google Scholar
• G. Klebe, U. Abraham, and T. Mietzner, Molecular similarity indices in a comparative analysis (CoMSIA) of drug molecules to correlate and predict their biological activity, J. Med. Chem. 37 (1994), pp. 4130–4146. doi:10.1021/jm00050a010.
   PubMed Web of Science ®Google Scholar
• S. Wold, A. Ruhe, H. Wold, and W.J. Dunn, The collinearity problem in linear regression. the partial least squares (PLS) approach to generalized inverses, SIAM J. Sci. Stat. Comput. 5 (1984), pp. 735–743. doi:10.1137/0905052.
   Web of Science ®Google Scholar
• P.C.D. Hawkins, A.G. Skillman, G.L. Warren, B.A. Ellingson, and M.T. Stahl, Conformer generation with OMEGA: Algorithm and validation using high quality structures from the protein databank and cambridge structural database, J. Chem. Inf. Model. 50 (2010), pp. 572–584. doi:10.1021/ci100031x.
   PubMed Web of Science ®Google Scholar
• P.C.D. Hawkins, A.G. Skillman, and A. Nicholls, Comparison of shape-matching and docking as virtual screening tools, J. Med. Chem. 50 (2007), pp. 74–82. doi:10.1021/jm0603365.
   PubMed Web of Science ®Google Scholar
• Sybyl X2.0. Drug design and discovery software; software Available at https://www.certara.com (accessed Feb, 2020).
   Google Scholar
• A. Golbraikh and A. Tropsha, Beware of q2! J. Mol. Graph. Model. 20 (2002), pp. 269–276. doi:10.1016/S1093-3263(01)00123-1.
   PubMed Web of Science ®Google Scholar
• A. Golbraikh, M. Shen, Z. Xiao, Y. De Xiao, K.H. Lee, and A. Tropsha, Rational selection of training and test sets for the development of validated QSAR models, J. Comput. Aided. Mol. Des. 17 (2003), pp. 241–253. doi:10.1023/A:1025386326946.
   PubMed Web of Science ®Google Scholar
• S.A. Wildman and G.M. Crippen, Prediction of physicochemical parameters by atomic contributions, J. Chem. Inf. Comput. Sci. 39 (1999), pp. 868–873. doi:10.1021/ci990307l.
   Google Scholar