Hydroxychloroquine Inhibits Zika Virus NS2B-NS3 Protease

ACS Omega

Volumn 3, Issue 12, 2018, Pages 18132-18141

  Kumar, Ankur ^a   Liang, Brooke ^b   Aarthy, Murali ^c   Singh, Sanjeev Kumar ^c   Garg, Neha ^a   Mysorekar, Indira U ^b   Giri, Rajanish ^a  

^a INDIAN INSTITUTE OF TECHNOLOGY MANDI   (India)

^b WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c ALAGAPPA UNIVERSITY   (India)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85059382470     PISSN: None     EISSN: 24701343     Source Type: Journal    
DOI: 10.1021/acsomega.8b01002     Document Type: Article

References (65)

1. Mlakar, J.; Korva, M.; Tul, N.; Popović, M.; Poljšak-Prijatelj, M.; Mraz, J.; Kolenc, M.; Resman Rus, K.; Vesnaver Vipotnik, T.; Fabjan Vodušek, V. et al. Zika Virus Associated with Microcephaly. N. Engl. J. Med. 2016, 374, 951-958, 10.1056/NEJMoa1600651
2. Rasmussen, S. A.; Jamieson, D. J.; Honein, M. A.; Petersen, L. R. Zika Virus and Birth Defects - Reviewing the Evidence for Causality. N. Engl. J. Med. 2016, 374, 1981-1987, 10.1056/NEJMsr1604338
3. Oehler, E.; Watrin, L.; Larre, P.; Leparc-Goffart, I.; Lastère, S.; Valour, F.; Baudouin, L.; Mallet, H. P.; Musso, D.; Ghawche, F. Zika Virus Infection Complicated by Guillain-Barré Syndrome-Case Report, French Polynesia, December 2013. Eurosurveillance 2014, 19, 20720 10.2807/1560-7917.ES2014.19.9.20720
4. Cao-Lormeau, V.-M.; Blake, A.; Mons, S.; Lastère, S.; Roche, C.; Vanhomwegen, J.; Dub, T.; Baudouin, L.; Teissier, A.; Larre, P. et al. Guillain-Barré Syndrome Outbreak Associated with Zika Virus Infection in French Polynesia: A Case-Control Study. Lancet 2016, 387, 1531-1539, 10.1016/S0140-6736(16)00562-6
5. Malkki, H. CNS Infections: Zika Virus Infection Could Trigger Guillain-Barré Syndrome. Nat. Rev. Neurol. 2016, 12, 187 10.1038/nrneurol.2016.30
6. Samarasekera, U.; Triunfol, M. Concern over Zika Virus Grips the World In the Past Week, the World Has Mobilised to Tackle the Latest Threat to Global Health Security. Lancet 2016, 387, 521-524, 10.1016/S0140-6736(16)00257-9
7. Sirohi, D.; Chen, Z.; Sun, L.; Klose, T.; Pierson, T. C.; Rossmann, M. G.; Kuhn, R. J. The 3.8 Å Resolution Cryo-EM Structure of Zika Virus. Science 2016, 352, 467-470, 10.1126/science.aaf5316
8. Kuno, G.; Chang, G.-J. J. Full-Length Sequencing and Genomic Characterization of Bagaza, Kedougou, and Zika Viruses. Arch. Virol. 2007, 152, 687-696, 10.1007/s00705-006-0903-z
9. Shiryaev, S. A.; Strongin, A. Y. Structural and Functional Parameters of the Flaviviral Protease: A Promising Antiviral Drug Target. Future Virol. 2010, 5, 593-606, 10.2217/fvl.10.39
10. Bollati, M.; Alvarez, K.; Assenberg, R.; Baronti, C.; Canard, B.; Cook, S.; Coutard, B.; Decroly, E.; de Lamballerie, X.; Gould, E. A. et al. Structure and Functionality in Flavivirus NS-Proteins: Perspectives for Drug Design. Antiviral Res. 2010, 87, 125-148, 10.1016/j.antiviral.2009.11.009
11. Erbel, P.; Schiering, N.; D'Arcy, A.; Renatus, M.; Kroemer, M.; Lim, S. P.; Yin, Z.; Keller, T. H.; Vasudevan, S. G.; Hommel, U. Structural Basis for the Activation of Flaviviral NS3 Proteases from Dengue and West Nile Virus. Nat. Struct. Mol. Biol. 2006, 13, 372-373, 10.1038/nsmb1073
12. Noble, C. G.; Seh, C. C.; Chao, A. T.; Shi, P. Y. Ligand-Bound Structures of the Dengue Virus Protease Reveal the Active Conformation. J. Virol. 2012, 86, 438-446, 10.1128/JVI.06225-11
13. Lei, J.; Hansen, G.; Nitsche, C.; Klein, C. D.; Zhang, L.; Hilgenfeld, R. Crystal Structure of Zika Virus NS2B-NS3 Protease in Complex with a Boronate Inhibitor. Science 2016, 353, 503-505, 10.1126/science.aag2419
14. Chen, X.; Yang, K.; Wu, C.; Chen, C.; Hu, C.; Buzovetsky, O.; Wang, Z.; Ji, X.; Xiong, Y.; Yang, H. Mechanisms of Activation and Inhibition of Zika Virus NS2B-NS3 Protease. Cell Res. 2016, 26, 1260-1263, 10.1038/cr.2016.116
15. Lee, H.; Ren, J.; Nocadello, S.; Rice, A. J.; Ojeda, I.; Light, S.; Minasov, G.; Vargas, J.; Nagarathnam, D.; Anderson, W. F. et al. Identification of Novel Small Molecule Inhibitors against NS2B/NS3 Serine Protease from Zika Virus. Antiviral Res. 2017, 139, 49-58, 10.1016/j.antiviral.2016.12.016
16. Giri, R.; Kumar, D.; Sharma, N.; Uversky, V. N. Intrinsically Disordered Side of the Zika Virus Proteome. Front. Cell. Infect. Microbiol. 2016, 6, 144 10.3389/fcimb.2016.00144
17. Mishra, P. M.; Uversky, V. N.; Giri, R. Molecular Recognition Features in Zika Virus Proteome. J. Mol. Biol. 2018, 430, 2372-2388, 10.1016/j.jmb.2017.10.018
18. Murray, C. L.; Jones, C. T.; Rice, C. M. Architects of Assembly: Roles of Flaviviridae Non-Structural Proteins in Virion Morphogenesis. Nat. Rev. Microbiol. 2008, 6, 699-708, 10.1038/nrmicro1928
19. Gianni, S.; Morrone, A.; Giri, R.; Brunori, M. A Folding-after-Binding Mechanism Describes the Recognition between the Transactivation Domain of c-Myb and the KIX Domain of the CREB-Binding Protein. Biochem. Biophys. Res. Commun. 2012, 428, 205-209, 10.1016/j.bbrc.2012.09.112
20. Giri, R.; Morrone, A.; Toto, A.; Brunori, M.; Gianni, S. Structure of the Transition State for the Binding of c-Myb and KIX Highlights an Unexpected Order for a Disordered System. Proc. Natl. Acad. Sci. U.S.A. 2013, 110, 14942-14947, 10.1073/pnas.1307337110
21. Toto, A.; Giri, R.; Brunori, M.; Gianni, S. The Mechanism of Binding of the KIX Domain to the Mixed Lineage Leukemia Protein and Its Allosteric Role in the Recognition of c-Myb. Protein Sci. 2014, 23, 962-969, 10.1002/pro.2480
22. Toto, A.; Camilloni, C.; Giri, R.; Brunori, M.; Vendruscolo, M.; Gianni, S. Molecular Recognition by Templated Folding of an Intrinsically Disordered Protein. Sci. Rep. 2016, 6, 21994 10.1038/srep21994
23. Patick, A. K.; Potts, K. E. Protease Inhibitors as Antiviral Agents. Clin. Microbiol. Rev. 1998, 11, 614-627, 10.1128/CMR.11.4.614
24. Anderson, J.; Schiffer, C.; Lee, S.-K.; Swanstrom, R. Viral Protease Inhibitors. In Antiviral Strategies; Springer: Berlin, Heidelberg, 2009; pp 85-110.
25. Tong, L. Viral Proteases. Chem. Rev. 2002, 102, 4609-4626, 10.1021/cr010184f
26. Yang, C.-C.; Hsieh, Y.-C.; Lee, S.-J.; Wu, S.-H.; Liao, C.-L.; Tsao, C.-H.; Chao, Y.-S.; Chern, J.-H.; Wu, C.-P.; Yueh, A. Novel Dengue Virus-Specific NS2B-NS3 Protease Inhibitor, BP2109, Discovered by a High-Throughput Screening Assay. Antimicrob. Agents Chemother. 2011, 55, 229-238, 10.1128/AAC.00855-10
27. Wu, H.; Bock, S.; Snitko, M.; Berger, T.; Weidner, T.; Holloway, S.; Kanitz, M.; Diederich, W. E.; Steuber, H.; Walter, C. et al. Novel Dengue Virus NS2B-NS3 Protease Inhibitors. Antimicrob. Agents Chemother. 2015, 59, 1100-1109, 10.1128/AAC.03543-14
28. Chan, J. F.-W.; Chik, K. K.-H.; Yuan, S.; Yip, C. C.-Y.; Zhu, Z.; Tee, K.-M.; Tsang, J. O.-L.; Chan, C. C.-S.; Poon, V. K.-M.; Lu, G. et al. Novel Antiviral Activity and Mechanism of Bromocriptine as a Zika Virus NS2B-NS3 Protease Inhibitor. Antiviral Res. 2017, 141, 29-37, 10.1016/j.antiviral.2017.02.002
29. Lin, K.-H.; Ali, A.; Rusere, L.; Soumana, D. I.; Kurt Yilmaz, N.; Schiffer, C. A. Dengue Virus NS2B-NS3 Protease Inhibitors Exploiting the Prime Side. J. Virol. 2017, 91, JVI-00045 10.1128/JVI.00045-17
30. Ashburn, T. T.; Thor, K. B. Drug Repositioning: Identifying and Developing New Uses for Existing Drugs. Nat. Rev. Drug Discovery 2004, 3, 673-683, 10.1038/nrd1468
31. Leung, D.; Schroder, K.; White, H.; Fang, N. X.; Stoermer, M. J.; Abbenante, G.; Martin, J. L.; Young, P. R.; Fairlie, D. P. Activity of Recombinant Dengue 2 Virus NS3 Protease in the Presence of a Truncated NS2B Co-Factor, Small Peptide Substrates, and Inhibitors. J. Biol. Chem. 2001, 276, 45762-45771, 10.1074/jbc.M107360200
32. Brecher, M.; Zhang, J.; Li, H. The Flavivirus Protease as a Target for Drug Discovery. Virol. Sin. 2013, 28, 326-336, 10.1007/s12250-013-3390-x
33. Li, Z.; Brecher, M.; Deng, Y. Q.; Zhang, J.; Sakamuru, S.; Liu, B.; Huang, R.; Koetzner, C. A.; Allen, C. A.; Jones, S. A. et al. Existing Drugs as Broad-Spectrum and Potent Inhibitors for Zika Virus by Targeting NS2B/NS3 Interaction. Cell Res. 2017, 27, 1046-1064, 10.1038/cr.2017.88
34. Cao, B.; Parnell, L. A.; Diamond, M. S.; Mysorekar, I. U. Inhibition of Autophagy Limits Vertical Transmission of Zika Virus in Pregnant Mice. J. Exp. Med. 2017, 214, 2303-2313, 10.1084/jem.20170957
35. Wang, L.-F.; Lin, Y.-S.; Huang, N.-C.; Yu, C.-Y.; Tsai, W.-L.; Chen, J.-J.; Kubota, T.; Matsuoka, M.; Chen, S.-R.; Yang, C.-S. et al. Hydroxychloroquine-Inhibited Dengue Virus Is Associated with Host Defense Machinery. J. Interferon Cytokine Res. 2015, 35, 143-156, 10.1089/jir.2014.0038
36. Sperber, K.; Hom, C.; Peng Chao, C.; Shapiro, D.; Ash, J.; Aberientos, C. Systematic Review of Hydroxychloroquine Use in Pregnant Patients with Autoimmune Diseases. Pediatric Rheumatol. 2009, 7, 9 10.1186/1546-0096-7-9
37. Costedoat-Chalumeau, N.; Amoura, Z.; Duhaut, P.; Huong, D. L. T.; Sebbough, D.; Wechsler, B.; Vauthier, D.; Denjoy, I.; Lupoglazoff, J.-M.; Piette, J.-C. Safety of Hydroxychloroquine in Pregnant Patients with Connective Tissue Diseases: A Study of One Hundred Thirty-Three Cases Compared with a Control Group. Arthritis Rheum. 2003, 48, 3207-3211, 10.1002/art.11304
38. Motta, M.; Tincani, A.; Faden, D.; Zinzini, E.; Lojacono, A.; Marchesi, A.; Frassi, M.; Biasini, C.; Zatti, S.; Chirico, G. Follow-Up of Infants Exposed to Hydroxychloroquine Given to Mothers during Pregnancy and Lactation. J. Perinatol. 2005, 25, 86-89, 10.1038/sj.jp.7211208
39. Yin, Y.; Xu, Y.; Su, L.; Zhu, X.; Chen, M.; Zhu, W.; Xia, H.; Huang, X.; Gong, S. Epidemiologic Investigation of a Family Cluster of Imported ZIKV Cases in Guangdong, China: Probable Human-to-Human Transmission. Emerging Microbes Infect. 2016, 5, e100 10.1038/emi.2016.100
40. Grischott, F.; Puhan, M.; Hatz, C.; Schlagenhauf, P. Non-Vector-Borne Transmission of Zika Virus: A Systematic Review. Travel Med. Infect. Disease 2016, 14, 313-330, 10.1016/j.tmaid.2016.07.002
41. Roberts, N.; Martin, J.; Kinchington, D.; Broadhurst, A.; Craig, J.; Duncan, I.; Galpin, S.; Handa, B.; Kay, J.; Krohn, A. et al. Rational Design of Peptide-Based HIV Proteinase Inhibitors. Science 1990, 248, 358-361, 10.1126/science.2183354
42. Bechtold, C. M.; Patick, A. K.; Alam, M.; Greytok, J.; Tino, J. A.; Chen, P.; Gordon, E.; Ahmad, S.; Barrish, J. C.; Zahler, R. Antiviral Properties of Aminodiol Inhibitors against Human Immunodeficiency Virus and Protease. Antimicrob. Agents Chemother. 1995, 39, 374-379, 10.1128/AAC.39.2.374
43. Yang, C. C.; Hu, H. S.; Wu, R. H.; Wu, S. H.; Lee, S. J.; Jiaang, W. T.; Chern, J. H.; Huang, Z. S.; Wu, H. N.; Chang, C. M. et al. A Novel Dengue Virus Inhibitor, BP13944, Discovered by High-Throughput Screening with Dengue Virus Replicon Cells Selects for Resistance in the Viral NS2B-NS3 Protease. Antimicrob. Agents Chemother. 2014, 58, 110-119, 10.1128/AAC.01281-13
44. Wu, H.; Bock, S.; Snitko, M.; Berger, T.; Weidner, T.; Holloway, S.; Kanitz, M.; Diederich, W. E.; Steuber, H.; Walter, C. et al. Novel Dengue Virus NS2B-NS3 Protease Inhibitors. Antimicrob. Agents Chemother. 2015, 59, 1100-1109, 10.1128/AAC.03543-14
45. Kouretova, J.; Hammamy, M. Z.; Epp, A.; Hardes, K.; Kallis, S.; Zhang, L.; Hilgenfeld, R.; Bartenschlager, R.; Steinmetzer, T. Effects of NS2B-NS3 Protease and Furin Inhibition on West Nile and Dengue Virus Replication. J. Enzyme Inhib. Med. Chem. 2017, 32, 712-721, 10.1080/14756366.2017.1306521
46. Nitsche, C.; Holloway, S.; Schirmeister, T.; Klein, C. D. Biochemistry and Medicinal Chemistry of the Dengue Virus Protease. Chem. Rev. 2014, 114, 11348-11381, 10.1021/cr500233q
47. Ekins, S.; Mietchen, D.; Coffee, M.; Stratton, T. P.; Freundlich, J. S.; Freitas-Junior, L.; Muratov, E.; Siqueira-Neto, J.; Williams, A. J.; Andrade, C. Open Drug Discovery for the Zika Virus. F1000Research 2016, 5, 150 10.12688/f1000research.8013.1
48. Gruba, N.; Ignacio, J.; Martinez, R.; Grzywa, R.; Wysocka, M. Substrate Profiling of Zika Virus NS2B-NS3 Protease. FEBS Lett. 2016, 590, 3459-3468, 10.1002/1873-3468.12443
49. Nitsche, C.; Zhang, L.; Weigel, L. F.; Schilz, J.; Graf, D.; Bartenschlager, R.; Hilgenfeld, R.; Klein, C. D. Peptide-Boronic Acid Inhibitors of Flaviviral Proteases: Medicinal Chemistry and Structural Biology. J. Med. Chem. 2017, 60, 511-516, 10.1021/acs.jmedchem.6b01021
50. Robin, G.; Chappell, K.; Stoermer, M. J.; Hu, S.-H.; Young, P. R.; Fairlie, D. P.; Martin, J. L. Structure of West Nile Virus NS3 Protease: Ligand Stabilization of the Catalytic Conformation. J. Mol. Biol. 2009, 385, 1568-1577, 10.1016/j.jmb.2008.11.026
51. Hammamy, M. Z.; Haase, C.; Hammami, M.; Hilgenfeld, R.; Steinmetzer, T. Development and Characterization of New Peptidomimetic Inhibitors of the West Nile Virus NS2B-NS3 Protease. ChemMedChem 2013, 8, 231-241, 10.1002/cmdc.201200497
52. Randolph, V. B.; Winkler, G.; Stollar, V. Acidotropic Amines Inhibit Proteolytic Processing of Flavivirus prM Protein. Virology 1990, 174, 450-458, 10.1016/0042-6822(90)90099-D
53. Delvecchio, R.; Higa, L.; Pezzuto, P.; Valadao, A.; Garcez, P.; Monteiro, F.; Loiola, E.; Dias, A.; Silva, F.; Aliota, M. et al. Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models. Viruses 2016, 8, 322 10.3390/v8120322
54. Rut, W.; Zhang, L.; Kasperkiewicz, P.; Poreba, M.; Hilgenfeld, R.; Drag, M. Extended Substrate Specificity and First Potent Irreversible Inhibitor/activity-Based Probe Design for Zika Virus NS2B-NS3 Protease. Antiviral Res. 2017, 139, 88-94, 10.1016/j.antiviral.2016.12.018
55. Law, V.; Knox, C.; Djoumbou, Y.; Jewison, T.; Guo, A. C.; Liu, Y.; Maciejewski, A.; Arndt, D.; Wilson, M.; Neveu, V. et al. DrugBank 4.0: Shedding New Light on Drug Metabolism. Nucleic Acids Res. 2014, 42, D1091-D1097, 10.1093/nar/gkt1068
56. Nabuurs, S. B.; Wagener, M.; de Vlieg, J. A Flexible Approach to Induced Fit Docking. J. Med. Chem. 2007, 50, 6507-6518, 10.1021/jm070593p
57. Gupta, S.; Suryanarayanan, V.; Yadav, S.; Singh, S. K.; Saxena, J. K. Delineating the Role of Ionic Interactions in Structural and Functional Integrity of B. malayi Guanylate Kinase. Int. J. Biol. Macromol. 2017, 98, 357-365, 10.1016/j.ijbiomac.2017.01.098
58. Gupta, S.; Yadav, S.; Suryanarayanan, V.; Singh, S. K.; Saxena, J. K. Investigating the Folding Pathway and Substrate Induced Conformational Changes in B. malayi Guanylate Kinase. Int. J. Biol. Macromol. 2017, 94, 621-633, 10.1016/j.ijbiomac.2016.10.008
59. Lenselink, E. B.; Louvel, J.; Forti, A. F.; van Veldhoven, J. P. D.; de Vries, H.; Mulder-Krieger, T.; McRobb, F. M.; Negri, A.; Goose, J.; Abel, R. et al. Predicting Binding Affinities for GPCR Ligands Using Free-Energy Perturbation. ACS Omega 2016, 1, 293-304, 10.1021/acsomega.6b00086
60. Gunasekaran, D.; Sridhar, J.; Suryanarayanan, V.; Manimaran, N. C.; Singh, S. K. Molecular Modeling and Structural Analysis of nAChR Variants Uncovers the Mechanism of Resistance to Snake Toxins. J. Biomol. Struct. Dyn. 2017, 35, 1654-1671, 10.1080/07391102.2016.1190791
61. Foloppe, N.; Chen, I.-J. Towards Understanding the Unbound State of Drug Compounds: Implications for the Intramolecular Reorganization Energy upon Binding. Bioorg. Med. Chem. 2016, 24, 2159-2189, 10.1016/j.bmc.2016.03.022
62. Dror, R. O.; Dirks, R. M.; Grossman, J. P.; Xu, H.; Shaw, D. E. Biomolecular Simulation: A Computational Microscope for Molecular Biology. Annu. Rev. Biophys. 2012, 41, 429-452, 10.1146/annurev-biophys-042910-155245
63. Sharma, N.; Murali, A.; Singh, S. K.; Giri, R. Epigallocatechin Gallate, an Active Green Tea Compound Inhibits the Zika Virus Entry into Host Cells via Binding the Envelope Protein. Int. J. Biol. Macromol. 2017, 104, 1046-1054, 10.1016/j.ijbiomac.2017.06.105
64. Miner, J. J.; Cao, B.; Govero, J.; Smith, A. M.; Fernandez, E.; Cabrera, O. H.; Garber, C.; Noll, M.; Klein, R. S.; Noguchi, K. K. et al. Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise. Cell 2016, 165, 1081-1091, 10.1016/j.cell.2016.05.008
65. Lanciotti, R. S.; Kosoy, O. L.; Laven, J. J.; Velez, J. O.; Lambert, A. J.; Johnson, A. J.; Stanfield, S. M.; Duffy, M. R. Genetic and Serologic Properties of Zika Virus Associated with an Epidemic, Yap State, Micronesia, 2007. Emerging Infect. Dis. 2008, 14, 1232-1239, 10.3201/eid1408.080287