Exploring the Targets of Dengue Virus and Designs of Potential Inhibitors


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Abstract

Background:Dengue, a mosquito-borne viral disease spread by the dengue virus (DENV), has become one of the most alarming health issues in the global scenario in recent days. The risk of infection by DENV is mostly high in tropical and subtropical areas of the world. The mortality rate of patients affected with DENV is ever-increasing, mainly due to a lack of anti-dengue viral-specific synthetic drug components.

Introduction:Repurposing synthetic drugs has been an effective tool in combating several pathogens, including DENV. However, only the Dengvaxia vaccine has been developed so far to fight against the deadly disease despite the grave situation, mainly because of the limitations of understanding the actual pathogenicity of the disease.

Methods:To address this particular issue and explore the actual disease pathobiology, several potential targets, like three structural proteins and seven non-structural (NS) proteins, along with their inhibitors of synthetic and natural origin, have been screened using docking simulation.

Results:Exploration of these targets, along with their inhibitors, has been extensively studied in culmination with molecular docking-based screening to potentiate the treatment.

Conclusion:These screened inhibitors could possibly be helpful for the designing of new congeneric potential compounds to combat dengue fever and its complications.

About the authors

Sayan Nath

Cell and Developmental Biology Special, Department of Zoology, University of Kalyani

Email: info@benthamscience.net

Piyali Malakar

Cell and Developmental Biology Special, Department of Zoology, University of Kalyani

Email: info@benthamscience.net

Baisakhi Biswas

Cell and Developmental Biology Special, Department of Zoology, University of Kalyani

Email: info@benthamscience.net

Suryatapa Das

Cell and Developmental Biology Special, Department of Zoology, University of Kalyani

Email: info@benthamscience.net

Nahid Sabnam

Cell and Developmental Biology Special, Department of Zoology, University of Kalyani

Email: info@benthamscience.net

Sisir Nandi

Global Institute of Pharmaceutical Education and Research, Veer Madho Singh Bhandari Uttarakhand Technical University

Author for correspondence.
Email: info@benthamscience.net

Asmita Samadder

Cell and Developmental Biology Special, Department of Zoology, University of Kalyani

Author for correspondence.
Email: info@benthamscience.net

References

  1. Perera, R.; Kuhn, R.J. Structural proteomics of dengue virus. Curr. Opin. Microbiol., 2008, 11(4), 369-377. doi: 10.1016/j.mib.2008.06.004 PMID: 18644250
  2. Potisopon, S.; Priet, S.; Collet, A.; Decroly, E.; Canard, B.; Selisko, B. The methyltransferase domain of dengue virus protein NS5 ensures efficient RNA synthesis initiation and elongation by the polymerase domain. Nucleic Acids Res., 2014, 42(18), 11642-11656. doi: 10.1093/nar/gku666 PMID: 25209234
  3. Seema; Jain, S.K. Molecular mechanism of pathogenesis of dengue virus: Entry and fusion with target cell. Indian J. Clin. Biochem., 2005, 20(2), 92-103. doi: 10.1007/BF02867407
  4. Kesorn, K.; Ongruk, P.; Chompoosri, J.; Phumee, A.; Thavara, U.; Tawatsin, A.; Siriyasatien, P. Morbidity rate prediction of Dengue Hemorrhagic Fever (DHF) using the support vector machine and the aedes aegypti infection rate in similar climates and geographical areas. PLoS One, 2015, 10(5), e0125049. doi: 10.1371/journal.pone.0125049 PMID: 25961289
  5. Chagas, G.C.L.; Rangel, A.R.; Noronh, L.M.; Veloso, F.C.S.; Kassar, S.B.; Oliveira, M.J.C.; Meneses, G.C.; da Silva, G.B. Junior; Daher, E.F. Risk factors for mortality in patients with dengue: A systematic review and meta-analysis. Trop. Med. Int. Health, 2022, 27(8), 656-668. doi: 10.1111/tmi.13797
  6. Srikiatkhachorn, A.; Rothman, A.L.; Gibbons, R.V.; Sittisombut, N.; Malasit, P.; Ennis, F.A.; Nimmannitya, S.; Kalayanarooj, S. Dengue--how best to classify it. Clin. Infect. Dis., 2011, 53(6), 563-567. doi: 10.1093/cid/cir451 PMID: 21832264
  7. Martina, B.E.E.; Koraka, P.; Osterhaus, A.D.M.E. Dengue virus pathogenesis: An integrated view. Clin. Microbiol. Rev., 2009, 22(4), 564-581. doi: 10.1128/CMR.00035-09 PMID: 19822889
  8. El Sahili, A.; Lescar, J. Dengue Virus Non-Structural Protein 5. Viruses, 2017, 9(4), 91. doi: 10.3390/v9040091 PMID: 28441781
  9. Bhatt, S.; Gething, P.W.; Brady, O.J.; Messina, J.P.; Farlow, A.W.; Moyes, C.L.; Drake, J.M.; Brownstein, J.S.; Hoen, A.G.; Sankoh, O.; Myers, M.F.; George, D.B.; Jaenisch, T.; Wint, G.R.W.; Simmons, C.P.; Scott, T.W.; Farrar, J.J.; Hay, S.I. The global distribution and burden of dengue. Nature, 2013, 496(7446), 504-507. doi: 10.1038/nature12060 PMID: 23563266
  10. Byk, L.A.; Gamarnik, A.V. Properties and functions of the dengue virus capsid protein. Annu. Rev. Virol., 2016, 3(1), 263-281. doi: 10.1146/annurev-virology-110615-042334 PMID: 27501261
  11. Mena Lora, A.J.; Fernandez, J.; Soto, Y.; Morales, A.; Brito, M.O.; Feris-Iglesias, J. Disease severity and mortality caused by dengue in a Dominican pediatric population. Am. J. Trop. Med. Hyg., 2014, 90(1), 169-172. doi: 10.4269/ajtmh.13-0440 PMID: 24218410
  12. Zeng, Z.; Zhan, J.; Chen, L.; Chen, H.; Cheng, S. Global, regional, and national dengue burden from 1990 to 2017: A systematic analysis based on the global burden of disease study 2017. EClinicalMedicine, 2021, 32, 100712. doi: 10.1016/j.eclinm.2020.100712 PMID: 33681736
  13. Rodenhuis-Zybert, I.A.; Wilschut, J.; Smit, J.M. Dengue virus life cycle: Viral and host factors modulating infectivity. Cell. Mol. Life Sci., 2010, 67(16), 2773-2786. doi: 10.1007/s00018-010-0357-z
  14. Sirisena, P.D.; Noordeen, F. Evolution of dengue in Sri Lanka-changes in the virus, vector, and climate. IJID, 2014, 19, 6-12. doi: 10.1016/j.ijid.2013.10.012
  15. Harapan, H.; Michie, A.; Sasmono, R.T.; Imrie, A. Dengue: A minireview. Viruses, 2020, 12(8), 829. doi: 10.3390/v12080829
  16. Nanaware, N.; Banerjee, A.; Mullick Bagchi, S.; Bagchi, P.; Mukherjee, A. Dengue virus infection: A tale of viral exploitations and host responses. Viruses, 2021, 13(10), 1967. doi: 10.3390/v13101967 PMID: 34696397
  17. Nature. Dengue virus structure. Available from: https://www.nature.com/scitable/content/dengue-virus-structure-22401481/
  18. Li, L.; Lok, S.M.; Yu, I.M.; Zhang, Y.; Kuhn, R.J.; Chen, J.; Rossmann, M.G. The flavivirus precursor membrane-envelope protein complex: Structure and maturation. Science, 2008, 319(5871), 1830-1834. doi: 10.1126/science.1153263 PMID: 18369147
  19. Yu, I.M.; Zhang, W.; Holdaway, H.A.; Li, L.; Kostyuchenko, V.A.; Chipman, P.R.; Kuhn, R.J.; Rossmann, M.G.; Chen, J. Structure of the immature dengue virus at low pH primes proteolytic maturation. Science, 2008, 319(5871), 1834-1837. doi: 10.1126/science.1153264 PMID: 18369148
  20. Modis, Y.; Ogata, S.; Clements, D.; Harrison, S.C. Structure of the dengue virus envelope protein after membrane fusion. Nature, 2004, 427(6972), 313-319. doi: 10.1038/nature02165 PMID: 14737159
  21. Roy, S.K.; Bhattacharjee, S. Dengue virus: Epidemiology, biology, and disease aetiology. Can. J. Microbiol., 2021, 67(10), 687-702. doi: 10.1139/cjm-2020-0572 PMID: 34171205
  22. Modis, Y.; Ogata, S.; Clements, D.; Harrison, S.C. A ligand-binding pocket in the dengue virus envelope glycoprotein. Proc. Natl. Acad. Sci., 2003, 100(12), 6986-6991. doi: 10.1073/pnas.0832193100 PMID: 12759475
  23. Fernandez-Garcia, M.D.; Mazzon, M.; Jacobs, M.; Amara, A. Pathogenesis of flavivirus infections: Using and abusing the host cell. Cell Host Microbe, 2009, 5(4), 318-328. doi: 10.1016/j.chom.2009.04.001 PMID: 19380111
  24. Jones, C.T.; Ma, L.; Burgner, J.W.; Groesch, T.D.; Post, C.B.; Kuhn, R.J. Flavivirus capsid is a dimeric alpha-helical protein. J. Virol., 2003, 77(12), 7143-7149. doi: 10.1128/JVI.77.12.7143-7149.2003 PMID: 12768036
  25. Balinsky, C.A.; Schmeisser, H.; Ganesan, S.; Singh, K.; Pierson, T.C.; Zoon, K.C. Nucleolin interacts with the dengue virus capsid protein and plays a role in formation of infectious virus particles. J. Virol., 2013, 87(24), 13094-13106. doi: 10.1128/JVI.00704-13 PMID: 24027323
  26. Ma, L.; Jones, C.T.; Groesch, T.D.; Kuhn, R.J.; Post, C.B. Solution structure of dengue virus capsid protein reveals another fold. Proc. Natl. Acad. Sci., 2004, 101(10), 3414-3419. doi: 10.1073/pnas.0305892101 PMID: 14993605
  27. Khromykh, A.A.; Varnavski, A.N.; Sedlak, P.L.; Westaway, E.G. Coupling between replication and packaging of flavivirus RNA: Evidence derived from the use of DNA-based full-length cDNA clones of Kunjin virus. J. Virol., 2001, 75(10), 4633-4640. doi: 10.1128/JVI.75.10.4633-4640.2001 PMID: 11312333
  28. Tseng, H.N.; Lee, C.C.; Wong, M.L.; Chen, S.O.; Liu, J.J. DNA-binding property of recombinant capsid protein of Japanese encephalitis virus. Virus Genes, 2007, 35(3), 483-488. doi: 10.1007/s11262-006-0075-7 PMID: 17957476
  29. Schrauf, S.; Mandl, C.W.; Bell-Sakyi, L.; Skern, T. Extension of flavivirus protein C differentially affects early RNA synthesis and growth in mammalian and arthropod host cells. J. Virol., 2009, 83(21), 11201-11210. doi: 10.1128/JVI.01025-09 PMID: 19692461
  30. Puttikhunt, C.; Keelapang, P.; Khemnu, N.; Sittisombut, N.; Kasinrerk, W.; Malasit, P. Novel anti-dengue monoclonal antibody recognizing conformational structure of the prM-E heterodimeric complex of dengue virus. J. Med. Virol., 2008, 80(1), 125-133. doi: 10.1002/jmv.21047 PMID: 18041028
  31. Netsawang, J.; Noisakran, S.; Puttikhunt, C.; Kasinrerk, W.; Wongwiwat, W.; Malasit, P.; Yenchitsomanus, P.; Limjindaporn, T. Nuclear localization of dengue virus capsid protein is required for DAXX interaction and apoptosis. Virus Res., 2010, 147(2), 275-283. doi: 10.1016/j.virusres.2009.11.012 PMID: 19944121
  32. Zhang, Y.; Zhang, W.; Ogata, S.; Clements, D.; Strauss, J.H.; Baker, T.S.; Kuhn, R.J.; Rossmann, M.G. Conformational changes of the flavivirus E glycoprotein. Structure, 2004, 12(9), 1607-1618. doi: 10.1016/j.str.2004.06.019
  33. De Paula, S.O.; Lima, D.M.; de Oliveira França, R.F.; Gomes-Ruiz, A.C.; da Fonseca, B.A.L. A DNA vaccine candidate expressing dengue-3 virus prM and E proteins elicits neutralizing antibodies and protects mice against lethal challenge. Arch. Virol., 2008, 153(12), 2215-2223. doi: 10.1007/s00705-008-0250-3 PMID: 19002647
  34. Rouvinski, A.; Guardado-Calvo, P.; Barba-Spaeth, G.; Duquerroy, S.; Vaney, M.C.; Kikuti, C.M.; Navarro Sanchez, M.E.; Dejnirattisai, W.; Wongwiwat, W.; Haouz, A.; Girard-Blanc, C.; Petres, S.; Shepard, W.E.; Desprès, P.; Arenzana-Seisdedos, F.; Dussart, P.; Mongkolsapaya, J.; Screaton, G.R.; Rey, F.A. Recognition determinants of broadly neutralizing human antibodies against dengue viruses. Nature, 2015, 520(7545), 109-113. doi: 10.1038/nature14130 PMID: 25581790
  35. Dharmapalan, B.T.; Biswas, R.; Sankaran, S.; Venkidasamy, B.; Thiruvengadam, M.; George, G.; Rebezov, M.; Zengin, G.; Gallo, M.; Montesano, D.; Naviglio, D.; Shariati, M.A. Inhibitory potential of chromene derivatives on structural and non-structural proteins of dengue virus. Viruses, 2022, 14(12), 2656. doi: 10.3390/v14122656 PMID: 36560664
  36. Lim, S.P.; Noble, C.G.; Shi, P.Y. The dengue virus NS5 protein as a target for drug discovery. Antiviral Res., 2015, 119, 57-67. doi: 10.1016/j.antiviral.2015.04.010
  37. Miller, S.; Kastner, S.; Krijnse-Locker, J.; Bühler, S.; Bartenschlager, R. The non-structural protein 4A of dengue virus is an integral membrane protein inducing membrane alterations in a 2K-regulated manner. J. Biol. Chem., 2007, 282(12), 8873-8882. doi: 10.1074/jbc.M609919200 PMID: 17276984
  38. Umareddy, I.; Chao, A.; Sampath, A.; Gu, F.; Vasudevan, S.G. Dengue virus NS4B interacts with NS3 and dissociates it from single-stranded RNA. J. Gen. Virol., 2006, 87(9), 2605-2614. doi: 10.1099/vir.0.81844-0 PMID: 16894199
  39. Othman, R.; Kiat, T.S.; Khalid, N.; Yusof, R.; Newhouse, E.I.; Newhouse, J.S.; Alam, M.; Rahman, N.A. Docking of noncompetitive inhibitors into dengue virus type 2 protease: Understanding the interactions with allosteric binding sites. J. Chem. Inf. Model., 2008, 48(8), 1583-1591.
  40. Wu, H.; Bock, S.; Snitko, M.; Berger, T.; Weidner, T.; Holloway, S.; Kanitz, M.; Diederich, W.E.; Steuber, H.; Walter, C.; Hofmann, D.; Weißbrich, B.; Spannaus, R.; Acosta, E.G.; Bartenschlager, R.; Engels, B.; Schirmeister, T.; Bodem, J. Novel dengue virus NS2B/NS3 protease inhibitors. Antimicrob. Agents Chemother., 2015, 59(2), 1100-1109. doi: 10.1128/AAC.03543-14 PMID: 25487800
  41. Yildiz, M.; Ghosh, S.; Bell, J.A.; Sherman, W.; Hardy, J.A. Allosteric inhibition of the NS2B-NS3 protease from dengue virus. ACS Chem. Biol., 2013, 8(12), 2744-2752. doi: 10.1021/cb400612h PMID: 24164286
  42. Lindenbach, B.D.; Thiel, H.J.; Rice, C.M. Flaviviridae: The viruses and their replication. In: Fields Virology, 5th ed; Knipe, D.M.; Howley, O.M., Eds.; Lippincot William & Wilkins: Philadelphia, 2011; pp. 1101-1151.
  43. Norazharuddin, H.; Lai, N.S. Roles and prospects of dengue virus nonstructural proteins as antiviral targets: An easy digest. Malays. J. Med. Sci., 2018, 25(5), 6-15. doi: 10.21315/mjms2018.25.5.2 PMID: 30914859
  44. Luo, D.; Vasudevan, S.G.; Lescar, J. The flavivirus NS2B-NS3 protease-helicase as a target for antiviral drug development. Antiviral Res., 2015, 118, 148-158. doi: 10.1016/j.antiviral.2015.03.014
  45. Luo, D.; Xu, T.; Hunke, C.; Grüber, G.; Vasudevan, S.G.; Lescar, J. Crystal structure of the NS3 protease-helicase from dengue virus. J. Virol., 2008, 82(1), 173-183.
  46. Xu, T.; Sampath, A.; Chao, A.; Wen, D.; Nanao, M.; Chene, P.; Vasudevan, S.G.; Lescar, J. Structure of the Dengue virus helicase/nucleoside triphosphatase catalytic domain at a resolution of 2.4 A. J. Virol., 2005, 79(16), 10278-10288. doi: 10.1128/JVI.79.16.10278-10288.2005 PMID: 16051821
  47. Gebhard, L.G.; Kaufman, S.B.; Gamarnik, A.V. Novel ATP-independent RNA annealing activity of the dengue virus NS3 helicase. PLoS One, 2012, 7(4), e36244. doi: 10.1371/journal.pone.0036244 PMID: 22558403
  48. Davidson, R.B.; Hendrix, J.; Geiss, B.J.; McCullagh, M. Allostery in the dengue virus NS3 helicase: Insights into the NTPase cycle from molecular simulations. PLOS Comput. Biol., 2018, 14(4), e1006103. doi: 10.1371/journal.pcbi.1006103 PMID: 29659571
  49. Lim, S.P.; Wang, Q.Y.; Noble, C.G.; Chen, Y.L.; Dong, H.; Zou, B.; Yokokawa, F.; Nilar, S.; Smith, P.; Beer, D.; Lescar, J.; Shi, P.Y. Ten years of dengue drug discovery: Progress and prospects. Antiviral Res., 2013, 100(2), 500-519. doi: 10.1016/j.antiviral.2013.09.013 PMID: 24076358
  50. Fairman-Williams, M.E.; Guenther, U.P.; Jankowsky, E. SF1 and SF2 helicases: Family matters. Curr. Opin. Struct. Biol., 2010, 20(3), 313-324. doi: 10.1016/j.sbi.2010.03.011 PMID: 20456941
  51. Luo, D.; Xu, T.; Watson, R.P.; Scherer-Becker, D.; Sampath, A.; Jahnke, W.; Yeong, S.S.; Wang, C.H.; Lim, S.P.; Strongin, A.; Vasudevan, S.G.; Lescar, J. Insights into RNA unwinding and ATP hydrolysis by the flavivirus NS3 protein. EMBO J., 2008, 27(23), 3209-3219. doi: 10.1038/emboj.2008.232 PMID: 19008861
  52. Chiang, P.Y.; Wu, H.N. The role of surface basic amino acids of dengue virus NS 3 helicase in viral RNA replication and enzyme activities. FEBS Lett., 2016, 590(14), 2307-2320. doi: 10.1002/1873-3468.12232 PMID: 27273003
  53. Li, X.D.; Shan, C.; Deng, C.L.; Ye, H.Q.; Shi, P.Y.; Yuan, Z.M.; Gong, P.; Zhang, B. The interface between methyltransferase and polymerase of NS5 is essential for flavivirus replication. PLoS Negl. Trop. Dis., 2014, 8(5), e2891. doi: 10.1371/journal.pntd.0002891 PMID: 24852307
  54. Yap, T.L.; Xu, T.; Chen, Y.L.; Malet, H.; Egloff, M.P.; Canard, B.; Vasudevan, S.G.; Lescar, J. Crystal structure of the dengue virus RNA-dependent RNA polymerase catalytic domain at 1.85-angstrom resolution. J. Virol., 2007, 81(9), 4753-4765. doi: 10.1128/JVI.02283-06 PMID: 17301146
  55. Lim, S.P.; Sonntag, L.S.; Noble, C.; Nilar, S.H.; Ng, R.H.; Zou, G.; Monaghan, P.; Chung, K.Y.; Dong, H.; Liu, B.; Bodenreider, C.; Lee, G.; Ding, M.; Chan, W.L.; Wang, G.; Jian, Y.L.; Chao, A.T.; Lescar, J.; Yin, Z.; Vedananda, T.R.; Keller, T.H.; Shi, P.Y. Small molecule inhibitors that selectively block dengue virus methyltransferase. J. Biol. Chem., 2011, 286(8), 6233-6240. doi: 10.1074/jbc.M110.179184 PMID: 21147775
  56. Issur, M.; Geiss, B.J.; Bougie, I.; Picard-Jean, F.; Despins, S.; Mayette, J.; Hobdey, S.E.; Bisaillon, M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA, 2009, 15(12), 2340-2350. doi: 10.1261/rna.1609709 PMID: 19850911
  57. Lu, G.; Gong, P. Crystal Structure of the full-length Japanese encephalitis virus NS5 reveals a conserved methyltransferase-polymerase interface. PLoS Pathog., 2013, 9(8), e1003549. doi: 10.1371/journal.ppat.1003549 PMID: 23950717
  58. Zhao, Y.; Soh, T.S.; Lim, S.P.; Chung, K.Y.; Swaminathan, K.; Vasudevan, S.G.; Shi, P.Y.; Lescar, J.; Luo, D. Molecular basis for specific viral RNA recognition and 2′-O-ribose methylation by the dengue virus nonstructural protein 5 (NS5). Proc. Natl. Acad. Sci., 2015, 112(48), 14834-14839. doi: 10.1073/pnas.1514978112 PMID: 26578813
  59. Benarroch, D.; Egloff, M.P.; Mulard, L.; Guerreiro, C.; Romette, J.L.; Canard, B. A structural basis for the inhibition of the NS5 dengue virus mRNA 2′-O-methyltransferase domain by ribavirin 5′-triphosphate. J. Biol. Chem., 2004, 279(34), 35638-35643. doi: 10.1074/jbc.M400460200 PMID: 15152003
  60. Idrus, S.; Tambunan, U.S.; Zubaidi, A.A. Designing cyclopentapeptide inhibitor as potential antiviral drug for dengue virus ns5 methyltransferase. Bioinformation, 2012, 8(8), 348-352.
  61. Lim, S.P.; Noble, C.G.; Seh, C.C.; Soh, T.S.; El Sahili, A.; Chan, G.K.; Lescar, J.; Arora, R.; Benson, T.; Nilar, S.; Manjunatha, U.; Wan, K.F.; Dong, H.; Xie, X.; Shi, P.Y.; Yokokawa, F. Potent allosteric dengue virus NS5 polymerase inhibitors: Mechanism of action and resistance profiling. PLoS Pathog., 2016, 12(8), e1005737.
  62. Obi, J.O.; Gutiérrez-Barbosa, H.; Chua, J.V.; Deredge, D.J. Current trends and limitations in dengue antiviral research. Trop. Med. Infect. Dis., 2021, 6(4), 180. doi: 10.3390/tropicalmed6040180
  63. Jia, H.; Gong, P. A structure-function diversity survey of the RNA-Dependent RNA polymerases from the positive-strand RNA viruses. Front. Microbiol., 1945, 2019(10), 31507560. doi: 10.3389/fmicb.2019.01945 PMID: 31507560
  64. Nncube, N.B.; Ramharack, P.; Soliman, M.E.S. Using bioinformatics tools for the discovery of Dengue RNA-dependent RNA polymerase inhibitors. Peer J., 2018, 6, e5068. doi: 10.7717/peerj.5068
  65. Ferrer-Orta, C.; Ferrero, D.; Verdaguer, N. RNA-Dependent RNA polymerases of picornaviruses: From the structure to regulatory mechanisms. Viruses., 2015, 7(8), 4438-4460.
  66. Venkataraman, S.; Prasad, B.V.L.S.; Selvarajan, R. RNA Dependent RNA polymerases: Insights from structure, function and evolution. Viruses, 2018, 10(2), 76.
  67. teVelthuis, A.J. Common and unique features of viral RNA-dependent polymerases. Cell. Mol. Life Sci., 2014, 71(22), 4430-4420.
  68. Černý, J. Evolution of tertiary structure of viral RNA dependent polymerases. PLoS One, 2014, 9(5), e96070.
  69. Jácome, R.; Becerra, A.; Ponce de León, S.; Lazcano, A. Structural analysis of monomeric RNA-dependent polymerases: Evolutionary and therapeutic implications. PLoS One, 2015, 10(9), e0139001.
  70. Garriga, D.; Ferrer-Orta, C.; Querol-Audi, J.; Oliva, B.; Verdaguer, N. Role of motif B loop in allosteric regulation of RNA-dependent RNA polymerization activity. J. Mol. Biol., 2013, 425(13), 2279-2287. doi: 10.1016/j.jmb.2013.03.034
  71. Wu, J.; Liu, W.; Gong, P. A structural overview of RNA-dependent RNA polymerases from the flaviviridae family. Int. J. Mol. Sci., 2015, 16(6), 12943-12957. doi: 10.3390/ijms160612943
  72. Behnam, M.A.M.; Nitsche, C.; Boldescu, V.; Klein, C.D. The medicinal chemistry of dengue virus. J. Med. Chem., 2016, 59(12), 5622-5649. doi: 10.1021/acs.jmedchem.5b01653 PMID: 26771861
  73. Byrd, C.M.; Dai, D.; Grosenbach, D.W.; Berhanu, A.; Jones, K.F.; Cardwell, K.B.; Schneider, C.; Wineinger, K.A.; Page, J.M.; Harver, C.; Stavale, E.; Tyavanagimatt, S.; Stone, M.A.; Bartenschlager, R.; Scaturro, P.; Hruby, D.E.; Jordan, R. A novel inhibitor of dengue virus replication that targets the capsid protein. Antimicrob. Agents Chemother., 2013, 57(1), 15-25. doi: 10.1128/AAC.01429-12 PMID: 23070172
  74. Xia, H.; Xie, X.; Zou, J.; Noble, C.G.; Russell, W.K.; Holthauzen, L.M.F.; Choi, K.H.; White, M.A.; Shi, P.Y. A cocrystal structure of dengue capsid protein in complex of inhibitor. Proc. Natl. Acad. Sci. USA, 2020, 117(30), 17992-18001. doi: 10.1073/pnas.2003056117 PMID: 32669438
  75. Smith, J.L.; Sheridan, K.; Parkins, C.J.; Frueh, L.; Jemison, A.L.; Strode, K.; Dow, G.; Nilsen, A.; Hirsch, A.J. Characterization and structure-activity relationship analysis of a class of antiviral compounds that directly bind dengue virus capsid protein and are incorporated into virions. Antiviral Res., 2018, 155, 12-19. doi: 10.1016/j.antiviral.2018.04.019 PMID: 29709563
  76. Faustino, A.F.; Guerra, G.M.; Huber, R.G.; Hollmann, A.; Domingues, M.M.; Barbosa, G.M.; Enguita, F.J.; Bond, P.J.; Castanho, M.A.R.B.; Da Poian, A.T.; Almeida, F.C.L.; Santos, N.C.; Martins, I.C. Understanding dengue virus capsid protein disordered N-Terminus and pep14-23-based inhibition. ACS Chem. Biol., 2015, 10(2), 517-526. doi: 10.1021/cb500640t PMID: 25412346
  77. Qin, C.F.; Qin, E.D. Development of cell lines stably expressing staphylococcal nuclease fused to dengue 2 virus capsid protein for CTVI. Acta Biochim. Biophys. Sin. (Shanghai), 2004, 36(8), 577-582. doi: 10.1093/abbs/36.8.577 PMID: 15295652
  78. De La Guardia, C.; Lleonart, R. Progress in the identification of dengue virus entry/fusion inhibitors. BioMed Res. Int., 2014, 2014, 1-13. doi: 10.1155/2014/825039 PMID: 25157370
  79. Melo, M.N.; Sousa, F.J.R.; Carneiro, F.A.; Castanho, M.A.R.B.; Valente, A.P.; Almeida, F.C.L.; Da Poian, A.T.; Mohana-Borges, R. Interaction of the Dengue virus fusion peptide with membranes assessed by NMR: The essential role of the envelope protein Trp101 for membrane fusion. J. Mol. Biol., 2009, 392(3), 736-746. doi: 10.1016/j.jmb.2009.07.035 PMID: 19619560
  80. Lin, Y.J.; Wu, S.C. Histidine at residue 99 and the transmembrane region of the precursor membrane prM protein are important for the prM-E heterodimeric complex formation of Japanese encephalitis virus. J. Virol., 2005, 79(13), 8535-8544. doi: 10.1128/JVI.79.13.8535-8544.2005 PMID: 15956595
  81. Roche, S.; Rey, F.A.; Gaudin, Y.; Bressanelli, S. Structure of the prefusion form of the vesicular stomatitis virus glycoprotein G. Science, 2007, 315(5813), 843-848. doi: 10.1126/science.1135710 PMID: 17289996
  82. Crill, W.D.; Roehrig, J.T. Monoclonal antibodies that bind to domain III of dengue virus E glycoprotein are the most efficient blockers of virus adsorption to Vero cells. J. Virol., 2001, 75(16), 7769-7773. doi: 10.1128/JVI.75.16.7769-7773.2001 PMID: 11462053
  83. Lin, S.R.; Zou, G.; Hsieh, S.C.; Qing, M.; Tsai, W.Y.; Shi, P.Y.; Wang, W.K. The helical domains of the stem region of dengue virus envelope protein are involved in both virus assembly and entry. J. Virol., 2011, 85(10), 5159-5171. doi: 10.1128/JVI.02099-10 PMID: 21367896
  84. Schmidt, A.G.; Lee, K.; Yang, P.L.; Harrison, S.C. Small-molecule inhibitors of dengue-virus entry. PLoS Pathog., 2012, 8(4), e1002627. doi: 10.1371/journal.ppat.1002627 PMID: 22496653
  85. Yang, J.M.; Chen, Y.F.; Tu, Y.Y.; Yen, K.R.; Yang, Y.L. Combinatorial computational approaches to identify tetracycline derivatives as flavivirus inhibitors. PLoS One, 2007, 2(5), e428. doi: 10.1371/journal.pone.0000428 PMID: 17502914
  86. Poh, M.K.; Yip, A.; Zhang, S.; Priestle, J.P.; Ma, N.L.; Smit, J.M.; Wilschut, J.; Shi, P.Y.; Wenk, M.R.; Schul, W. A small molecule fusion inhibitor of dengue virus. Antiviral Res., 2009, 84(3), 260-266. doi: 10.1016/j.antiviral.2009.09.011 PMID: 19800368
  87. Wang, Q.Y.; Patel, S.J.; Vangrevelinghe, E.; Xu, H.Y.; Rao, R.; Jaber, D.; Schul, W.; Gu, F.; Heudi, O.; Ma, N.L.; Poh, M.K.; Phong, W.Y.; Keller, T.H.; Jacoby, E.; Vasudevan, S.G. A small-molecule dengue virus entry inhibitor. Antimicrob. Agents Chemother., 2009, 53(5), 1823-1831. doi: 10.1128/AAC.01148-08 PMID: 19223625
  88. Leal, E.S.; Adler, N.S.; Fernández, G.A.; Gebhard, L.G.; Battini, L.; Aucar, M.G.; Videla, M.; Monge, M.E.; Hernández de los Ríos, A.; Acosta Dávila, J.A.; Morell, M.L.; Cordo, S.M.; García, C.C.; Gamarnik, A.V.; Cavasotto, C.N.; Bollini, M. De novo design approaches targeting an envelope protein pocket to identify small molecules against dengue virus. Eur. J. Med. Chem., 2019, 182111628. doi: 10.1016/j.ejmech.2019.111628 PMID: 31472473
  89. Zhou, Z.; Khaliq, M.; Suk, J.E.; Patkar, C.; Li, L.; Kuhn, R.J.; Post, C.B. Antiviral compounds discovered by virtual screening of small-molecule libraries against dengue virus E protein. ACS Chem. Biol., 2008, 3(12), 765-775. doi: 10.1021/cb800176t PMID: 19053243
  90. Kampmann, T.; Yennamalli, R.; Campbell, P.; Stoermer, M.J.; Fairlie, D.P.; Kobe, B.; Young, P.R. In silico screening of small molecule libraries using the dengue virus envelope E protein has identified compounds with antiviral activity against multiple flaviviruses. Antiviral Res., 2009, 84(3), 234-241. doi: 10.1016/j.antiviral.2009.09.007 PMID: 19781577
  91. Kaptein, S.J.F.; De Burghgraeve, T.; Froeyen, M.; Pastorino, B.; Alen, M.M.F.; Mondotte, J.A.; Herdewijn, P.; Jacobs, M.; de Lamballerie, X.; Schols, D.; Gamarnik, A.V.; Sztaricskai, F.; Neyts, J. A derivate of the antibiotic doxorubicin is a selective inhibitor of dengue and yellow fever virus replication in vitro. Antimicrob. Agents Chemother., 2010, 54(12), 5269-5280. doi: 10.1128/AAC.00686-10 PMID: 20837762
  92. Li, Z.; Khaliq, M.; Zhou, Z.; Post, C.B.; Kuhn, R.J.; Cushman, M. Design, synthesis, and biological evaluation of antiviral agents targeting flavivirus envelope proteins. J. Med. Chem., 2008, 51(15), 4660-4671. doi: 10.1021/jm800412d PMID: 18610998
  93. Jadav, S.S.; Kaptein, S.; Timiri, A.; De Burghgraeve, T.; Badavath, V.N.; Ganesan, R.; Sinha, B.N.; Neyts, J.; Leyssen, P.; Jayaprakash, V. Design, synthesis, optimization and antiviral activity of a class of hybrid dengue virus E protein inhibitors. Bioorg. Med. Chem. Lett., 2015, 25(8), 1747-1752. doi: 10.1016/j.bmcl.2015.02.059 PMID: 25791449
  94. Abdul Ahmad, S.A.; Palanisamy, U.D.; Tejo, B.A.; Chew, M.F.; Tham, H.W.; Syed Hassan, S. Geraniin extracted from the rind of Nephelium lappaceum binds to dengue virus type-2 envelope protein and inhibits early stage of virus replication. Virol. J., 2017, 14(1), 229. doi: 10.1186/s12985-017-0895-1 PMID: 29162124
  95. Kato, D.; Era, S.; Watanabe, I.; Arihara, M.; Sugiura, N.; Kimata, K.; Suzuki, Y.; Morita, K.; Hidari, K.I.P.J.; Suzuki, T. Antiviral activity of chondroitin sulphate E targeting dengue virus envelope protein. Antiviral Res., 2010, 88(2), 236-243. doi: 10.1016/j.antiviral.2010.09.002 PMID: 20851716
  96. Marks, R.M.; Lu, H.; Sundaresan, R.; Toida, T.; Suzuki, A.; Imanari, T.; Hernáiz, M.J.; Linhardt, R.J. Probing the interaction of dengue virus envelope protein with heparin: assessment of glycosaminoglycan-derived inhibitors. J. Med. Chem., 2001, 44(13), 2178-2187. doi: 10.1021/jm000412i PMID: 11405655
  97. Hidari, K.I.P.J.; Takahashi, N.; Arihara, M.; Nagaoka, M.; Morita, K.; Suzuki, T. Structure and anti-dengue virus activity of sulfated polysaccharide from a marine alga. Biochem. Biophys. Res. Commun., 2008, 376(1), 91-95. doi: 10.1016/j.bbrc.2008.08.100 PMID: 18762172
  98. Lee, E.; Pavy, M.; Young, N.; Freeman, C.; Lobigs, M. Antiviral effect of the heparan sulfate mimetic, PI-88, against dengue and encephalitic flaviviruses. Antiviral Res., 2006, 69(1), 31-38. doi: 10.1016/j.antiviral.2005.08.006 PMID: 16309754
  99. Talarico, L.B.; Damonte, E.B. Interference in dengue virus adsorption and uncoating by carrageenans. Virology, 2007, 363(2), 473-485. doi: 10.1016/j.virol.2007.01.043 PMID: 17337028
  100. Lin, L.T.; Chen, T.Y.; Lin, S.C.; Chung, C.Y.; Lin, T.C.; Wang, G.H.; Anderson, R.; Lin, C.C.; Richardson, C.D. Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entry. BMC Microbiol., 2013, 13(1), 187. doi: 10.1186/1471-2180-13-187 PMID: 23924316
  101. Scaturro, P.; Trist, I.M.L.; Paul, D.; Kumar, A.; Acosta, E.G.; Byrd, C.M.; Jordan, R.; Brancale, A.; Bartenschlager, R. Characterization of the mode of action of a potent dengue virus capsid inhibitor. J. Virol., 2014, 88(19), 11540-11555. doi: 10.1128/JVI.01745-14 PMID: 25056895
  102. Rothan, H.A.; Han, H.C.; Ramasamy, T.S.; Othman, S.; Rahman, N.A.; Yusof, R. Inhibition of dengue NS2B-NS3 protease and viral replication in Vero cells by recombinant retrocyclin-1. BMC Infect. Dis., 2012, 12, 314. doi: 10.1186/1471-2334-12-314
  103. Raut, R.; Beesetti, H.; Tyagi, P.; Khanna, I.; Jain, S.K.; Jeankumar, V.U.; Yogeeswari, P.; Sriram, D.; Swaminathan, S. A small molecule inhibitor of dengue virus type 2 protease inhibits the replication of all four dengue virus serotypes in cell culture. Virol. J., 2015, 12, 16. doi: 10.1186/s12985-015-0248-x
  104. Beesetti, H.; Tyagi, P.; Medapi, B.; Krishna, V.S.; Sriram, D.; Khanna, N.; Swaminathan, S. A quinoline compound inhibits the replication of dengue virus serotypes 1-4 in Vero cells. Antivir. Ther., 2018, 23(5), 385-394.
  105. Wu, D.; Mao, F.; Ye, Y.; Li, J.; Xu, C.; Luo, X.; Chen, J.; Shen, X. Policresulen, a novel NS2B/NS3 protease inhibitor, effectively inhibits the replication of DENV2 virus in BHK-21 cells. Acta Pharmacol. Sin., 2015, 36(9), 1126-1136. doi: 10.1038/aps.2015.56 PMID: 26279156
  106. 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.; Yueh, A. 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(1), 110-119. doi: 10.1128/AAC.01281-13 PMID: 24145533
  107. García, L.L.; Padilla, L.; Castaño, J.C. Inhibitors compounds of the flavivirus replication process. Virol. J., 2017, 14(1), 95. doi: 10.1186/s12985-017-0761-1
  108. Steuer, C.; Gege, C.; Fischl, W.; Heinonen, K.H.; Bartenschlager, R.; Klein, C.D. Synthesis and biological evaluation of α-ketoamides as inhibitors of the Dengue virus protease with antiviral activity in cell-culture. Bioorg. Med. Chem., 2011, 19(13), 4067-4074. doi: 10.1016/j.bmc.2011.05.015 PMID: 21641807
  109. Brecher, M.; Li, Z.; Liu, B.; Zhang, J.; Koetzner, C.A.; Alifarag, A.; Jones, S.A.; Lin, Q.; Kramer, L.D.; Li, H. A conformational switch high-throughput screening assay and allosteric inhibition of the flavivirus NS2B-NS3 protease. PLoS Pathog., 2017, 13(5), e1006411. doi: 10.1371/journal.ppat.1006411 PMID: 28542603
  110. Timiri, A.K.; Selvarasu, S.; Kesherwani, M.; Vijayan, V.; Sinha, B.N.; Devadasan, V.; Jayaprakash, V. Synthesis and molecular modelling studies of novel sulphonamide derivatives as dengue virus 2 protease inhibitors. Bioorg. Chem., 2015, 62, 74-82. doi: 10.1016/j.bioorg.2015.07.005 PMID: 26247308
  111. Pambudi, S.; Kawashita, N.; Phanthanawiboon, S.; Omokoko, M.D.; Masrinoul, P.; Yamashita, A.; Limkittikul, K.; Yasunaga, T.; Takagi, T.; Ikuta, K.; Kurosu, T. A small compound targeting the interaction between nonstructural proteins 2B and 3 inhibits dengue virus replication. Biochem. Biophys. Res. Commun., 2013, 440(3), 393-398. doi: 10.1016/j.bbrc.2013.09.078 PMID: 24070610
  112. Shin, H.J.; Kim, M.H.; Lee, J.Y.; Hwang, I.; Yoon, G.Y.; Kim, H.S.; Kwon, Y.C.; Ahn, D.G.; Kim, K.D.; Kim, B.T.; Kim, S.J.; Kim, C. Structure-based virtual screening: Identification of a novel NS2B-NS3 protease inhibitor with potent antiviral activity against zika and dengue viruses. Microorganisms, 2021, 9(3), 545. doi: 10.3390/microorganisms9030545 PMID: 33800763
  113. Saleem, H.N.; Batool, F.; Mansoor, H.J. Inhibition of dengue virus protease by eugeniin, isobiflorin, and biflorin isolated from the flower buds of syzygiumaromaticum (Cloves). ACS Omega, 2019, 4(1), 1525-1533. doi: 10.1021/acsomega.8b02861
  114. Ganji, L.V.; Kanyalkar, M.A. Non-structural proteases as a target of dengue virus. J. Antivir. Antiretrovir., 2019, 11, 188. doi: 10.35248/1948-5964.19.11.188
  115. Basavannacharya, C.; Vasudevan, S.G. Suramin inhibits helicase activity of NS3 protein of dengue virus in a fluorescence-based high throughput assay format. Biochem. Biophys. Res. Commun., 2014, 453(3), 539-544. doi: 10.1016/j.bbrc.2014.09.113 PMID: 25281902
  116. Byrd, C.M.; Grosenbach, D.W.; Berhanu, A.; Dai, D.; Jones, K.F.; Cardwell, K.B.; Schneider, C.; Yang, G.; Tyavanagimatt, S.; Harver, C.; Wineinger, K.A.; Page, J.; Stavale, E.; Stone, M.A.; Fuller, K.P.; Lovejoy, C.; Leeds, J.M.; Hruby, D.E.; Jordan, R. Novel benzoxazole inhibitor of dengue virus replication that targets the NS3 helicase. Antimicro. Agents Chemothera., 2013, 57(4), 1902-1912. doi: 10.1128/AAC.02251-12
  117. Felicetti, T.; Manfroni, G.; Cecchetti, V.; Cannalire, R. Broad-spectrum flavivirus inhibitors: A medicinal chemistry point of view. ChemMedChem, 2020, 15(24), 2391-2419. doi: 10.1002/cmdc.202000464
  118. Sweeney, N.L.; Hanson, A.M.; Mukherjee, S.; Ndjomou, J.; Geiss, B.J.; Steel, J.J.; Frankowski, K.J.; Li, K.; Schoenen, F.J.; Frick, D.N. Benzothiazole and pyrrolone flavivirus inhibitors targeting the viral helicase. ACS Infect. Dis., 2015, 1(3), 140-148. doi: 10.1021/id5000458 PMID: 26029739
  119. Kim, J.; Park, S.J.; Park, J.; Shin, H.; Jang, Y.S.; Woo, J.S.; Min, D.H. Identification of a direct-acting antiviral agent targeting RNA helicase via a graphene oxide nanobiosensor. ACS Appl. Mater. Interfaces, 2021, 13(22), 25715-25726. doi: 10.1021/acsami.1c04641 PMID: 34036784
  120. Mastrangelo, E.; Pezzullo, M.; De Burghgraeve, T.; Kaptein, S.; Pastorino, B.; Dallmeier, K.; de Lamballerie, X.; Neyts, J.; Hanson, A.M.; Frick, D.N.; Bolognesi, M.; Milani, M. Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: New prospects for an old drug. J. Antimicrob. Chemother., 2012, 67(8), 1884-1894. doi: 10.1093/jac/dks147 PMID: 22535622
  121. Nandi, S.; Naaz, A.; Saxena, M. Repurposing of potent mtase inhibitors against ZIKV utilizing structure-based molecular docking. Int. J. Quantit. Struct.- Property Relation., 2020, 5(4), 53-68. doi: 10.4018/IJQSPR.2020100103
  122. Chen, H.; Zhou, B.; Brecher, M.; Banavali, N.; Jones, S.A.; Li, Z.; Zhang, J.; Nag, D.; Kramer, L.D.; Ghosh, A.K.; Li, H. S-adenosyl-homocysteine is a weakly bound inhibitor for a flaviviral methyltransferase. PLoS One, 2013, 8(10), e76900. doi: 10.1371/journal.pone.0076900 PMID: 24130807
  123. Luzhkov, V.B.; Selisko, B.; Nordqvist, A.; Peyrane, F.; Decroly, E.; Alvarez, K.; Karlen, A.; Canard, B.; Åqvist, J. Virtual screening and bioassay study of novel inhibitors for dengue virus mRNA cap (nucleoside-2′O)-methyltransferase. Bioorg. Med. Chem., 2007, 15(24), 7795-7802. doi: 10.1016/j.bmc.2007.08.049 PMID: 17888664
  124. Milani, M.; Mastrangelo, E.; Bollati, M.; Selisko, B.; Decroly, E.; Bouvet, M.; Canard, B.; Bolognesi, M. Flaviviral methyltransferase/RNA interaction: Structural basis for enzyme inhibition. Antiviral Res., 2009, 83(1), 28-34. doi: 10.1016/j.antiviral.2009.03.001 PMID: 19501254
  125. Podvinec, M.; Lim, S.P.; Schmidt, T.; Scarsi, M.; Wen, D.; Sonntag, L.S.; Sanschagrin, P.; Shenkin, P.S.; Schwede, T. Novel inhibitors of dengue virus methyltransferase: Discovery by in vitro-driven virtual screening on a desktop computer grid. J. Med. Chem., 2010, 53(4), 1483-1495. doi: 10.1021/jm900776m PMID: 20108931
  126. P.W., Eaf; M., Ambre; P.K., Mandan; S., Coutinho Update on methyltransferase inhibitors of the dengue virus and further scope in the field. J. Emerg. Infect. Dis., 2016, 1(2), 108. doi: 10.4172/2472-4998.1000108
  127. Yadav, M.K.; Park, S.W.; Chae, S.W.; Song, J.J. Sinefungin, a natural nucleoside analogue of S-adenosylmethionine, inhibits streptococcus pneumoniae biofilm growth. BioMed Res. Int., 2014, 2014, 156987. doi: 10.1155/2014/156987
  128. Xu, T.L.; Han, Y.; Liu, W.; Pang, X.Y.; Zheng, B.; Zhang, Y.; Zhou, X.N. Antivirus effectiveness of ivermectin on dengue virus type 2 in Aedes albopictus. PLoS Negl. Trop. Dis., 2018, 12(11), e0006934. doi: 10.1371/journal.pntd.0006934 PMID: 30452439
  129. Zhang, X.; Ge, P.; Yu, X.; Brannan, J.M.; Bi, G.; Zhang, Q.; Schein, S.; Zhou, Z.H. Cryo-EM structure of the mature dengue virus at 3.5-Å resolution. Nat. Struct. Mol. Biol., 2013, 20(1), 102-110.
  130. Oliveira, A.S.; Silva, M.L.; Oliveira, A.F.C.S.; Silva, C.C.; Teixeira, R.R.; De Paula, S.O.; De Paula, S.O. NS3 and NS5 proteins: Important targets for anti-dengue drug design. J. Braz. Chem. Soc., 2014, 25(10), 1759-1769. doi: 10.5935/0103-5053.20140057
  131. Natali, E.N.; Babrak, L.M.; Miho, E. Prospective artificial intelligence to dissect the dengue immune response and discover therapeutics. Front. Immunol., 2021, 12, 574411. doi: 10.3389/fimmu.2021.574411 PMID: 34211454
  132. De Clercq, E.; Neyts, J. Antiviral agents acting as DNA or RNA chain terminators. Handb. Exp. Pharmacol., 2009, 189, 53-84. doi: 10.1007/978-3-540-79086-0_3
  133. Choi, K.H.; Rossmann, M.G. RNA-dependent RNA polymerases from flaviviridae. Curr. Opin. Struct. Biol., 2009, 19(6), 746-751. doi: 10.1016/j.sbi.2009.10.015
  134. De Francesco, R.; Tomei, L.; Altamura, S.; Summa, V.; Migliaccio, G. Approaching a new era for hepatitis C virus therapy: Inhibitors of the NS3-4A serine protease and the NS5B RNA-dependent RNA polymerase. Antiviral Res., 2003, 58(1), 1-16. doi: 10.1016/S0166-3542(03)00028-7
  135. Patil, V.M.; Balasubramanian, K.; Masand, N. Dengue virus polymerase: A crucial target for antiviral drug discovery. Viral Polymerase, 2019, 387-428. doi: 10.1016/B978-0-12-815422-9.00014-0
  136. Arora, R.; Liew, C.W.; Soh, T.S.; Otoo, D.A.; Seh, C.C.; Yue, K.; Nilar, S.; Wang, G.; Yokokawa, F.; Noble, C.G.; Chen, Y.L.; Shi, P.Y.; Lescar, J.; Smith, T.M.; Benson, T.E.; Lim, S.P. Two RNA tunnel inhibitors bind in highly conserved sites in dengue virus ns5 polymerase: Structural and functional studies. J. Virol., 2020, 94(24), e01130-e01120.
  137. Shimizu, H.; Saito, A.; Mikuni, J.; Nakayama, E.E.; Koyama, H.; Honma, T.; Shirouzu, M.; Sekine, S.I.; Shioda, T. Discovery of a small molecule inhibitor targeting dengue virus NS5 RNA-dependent RNA polymerase. PLoS Negl. Trop. Dis., 2019, 13(11), e0007894. doi: 10.1371/journal.pntd.0007894
  138. Yao, X.; Guo, S.; Wu, W.; Wang, J.; Wu, S.; He, S.; Wan, Y.; Nandakumar, K.S.; Chen, X.; Sun, N.; Zhu, Q.; Liu, S. Q63, a novel DENV2 RdRp non-nucleoside inhibitor, inhibited DENV2 replication and infection. J. Pharmacol. Sci., 2018, 138(4), 247-256. doi: 10.1016/j.jphs.2018.06.012
  139. Noble, C.G.; Lim, S.P.; Chen, Y.L.; Liew, C.W.; Yap, L.; Lescar, J.; Shi, P.Y. Conformational flexibility of the Dengue virus RNA-dependent RNA polymerase revealed by a complex with an inhibitor. J. Virol., 2013, 87(9), 5291-5295. doi: 10.1128/JVI.00045-13 PMID: 23408636
  140. Xu, H.T.; Colby-Germinario, S.P.; Hassounah, S.; Quashie, P.K.; Han, Y.; Oliveira, M.; Stranix, B.R.; Wainberg, M.A. Identification of a pyridoxine-derived small-molecule inhibitor targeting dengue virus RNA-dependent RNA polymerase. Antimicrob. Agents Chemothera., 2015, 60(1), 600-608.
  141. Yin, Z.; Chen, Y.L.; Schul, W.; Wang, Q.Y.; Gu, F.; Duraiswamy, J.; Kondreddi, R.R.; Niyomrattanakit, P.; Lakshminarayana, S.B.; Goh, A.; Xu, H.Y.; Liu, W.; Liu, B.; Lim, J.Y.; Ng, C.Y.; Qing, M.; Lim, C.C.; Yip, A.; Wang, G.; Chan, W.L. An adenosine nucleoside inhibitor of dengue virus. Proc. Natl. Acad. Sci., 2009, 20435-20439.
  142. Tarantino, D.; Cannalire, R.; Mastrangelo, E.; Croci, R.; Querat, G.; Barreca, M.L.; Bolognesi, M.; Manfroni, G.; Cecchetti, V.; Milani, M. Targeting flavivirus RNA dependent RNA polymerase through a pyridobenzothiazole inhibitor. Antiviral Res., 2016, 134, 226-235. doi: 10.1016/j.antiviral.2016.09.007 PMID: 27649989
  143. Tian, Y.S.; Zhou, Y.; Takagi, T.; Kameoka, M.; Kawashita, N. Dengue virus and its inhibitors: A brief review. Chem. Pharm. Bull., 2018, 66(3), 191-206. doi: 10.1248/cpb.c17-00794 PMID: 29491253
  144. Tambunan, U.S.F.; Noors, R.S.; Parikesit, A.A. Molecular dynamics simulation of DENV RNA-dependent RNA-polymerase with potential inhibitor of disulfide cyclic peptide. Online J. Biol. Sci., 2011, 11(2), 48-62. doi: 10.3844/ojbsci.2011.48.62
  145. Noble, C.G.; Lim, S.P.; Arora, R.; Yokokawa, F.; Nilar, S.; Seh, C.C.; Wright, S.K.; Benson, T.E.; Smith, P.W.; Shi, P.Y. A conserved pocket in the dengue virus polymerase identified through fragment-based screening. J. Biol. Chem., 2016, 291(16), 8541-8548. doi: 10.1074/jbc.M115.710731 PMID: 26872970
  146. Pelliccia, S.; Wu, Y.H.; Coluccia, A.; La Regina, G.; Tseng, C.K.; Famiglini, V.; Masci, D.; Hiscott, J.; Lee, J.C.; Silvestri, R. Inhibition of dengue virus replication by novel inhibitors of RNA-dependent RNA polymerase and protease activities. J. Enzyme Inhib. Med. Chem., 2017, 32(1), 1091-1101. doi: 10.1080/14756366.2017.1355791 PMID: 28776445
  147. Niyomrattanakit, P.; Chen, Y.L.; Dong, H.; Yin, Z.; Qing, M.; Glickman, J.F.; Lin, K.; Mueller, D.; Voshol, H.; Lim, J.Y.; Nilar, S.; Keller, T.H.; Shi, P.Y. Inhibition of dengue virus polymerase by blocking of the RNA tunnel. J. Virol., 2010, 84(11), 5678-5686. doi: 10.1128/JVI.02451-09
  148. Yokokawa, F.; Nilar, S.; Noble, C.G.; Lim, S.P.; Rao, R.; Tania, S.; Wang, G.; Lee, G.; Hunziker, J.; Karuna, R.; Manjunatha, U.; Shi, P.Y.; Smith, P.W. Discovery of potent non-nucleoside inhibitors of dengue viral RNA-dependent RNA polymerase from a fragment hit using structure-based drug design. J. Med. Chem., 2016, 59(8), 3935-3952. doi: 10.1021/acs.jmedchem.6b00143 PMID: 26984786
  149. Coulerie, P.; Maciuk, A.; Eydoux, C.; Hnawia, E.; Lebouvier, N.; Figadère, B.; Guillemot, J.C.; Nour, M. New inhibitors of the DENV-NS5 RdRp from carpolepis laurifolia as potential antiviral drugs for dengue treatment. ACG PUBLICATIONS Rec. Nat. Prod, 2014, 8(3), 286-289.
  150. Lavanya, P.; Ramaiah, S.; Anbarasu, A. Computational analysis reveal inhibitory action of nimbin against dengue viral envelope protein. Virusdisease, 2015, 26(4), 243-254. doi: 10.1007/s13337-015-0280-x PMID: 26645034
  151. Parida, M.M.; Upadhyay, C.; Pandya, G.; Jana, A.M. Inhibitory potential of neem (Azadirachta indica Juss) leaves on dengue virus type-2 replication. J. Ethnopharmacol., 2002, 79(2), 273-278.
  152. Ahmad, N.; Fazal, H.; Ayaz, M.; Abbasi, B.H.; Mohammad, I.; Fazal, L. Dengue fever treatment with Carica papaya leaves extracts. Asian Pac. J. Trop. Biomed., 2011, 1(4), 330-333. doi: 10.1016/S2221-1691(11)60055-5
  153. Sarker, M.M.R.; Khan, F.; Mohamed, I.N. Dengue fever: Therapeutic potential of carica papaya L. leaves. Front. Pharmacol., 2021, 12, 610912.
  154. Krishnasamy, K.K.; Ramalingam, S.; Karupannan, S.; Padmanaban, P.; Vijayan, S.; Sheriff, K.; Palani, G. Anti-dengue activity of Andrographis paniculata extracts and quantification of dengue viral inhibition by SYBR green reverse transcription polymerase chain reaction. Ayu, 2018, 39(2), 87-91. doi: 10.4103/ayu.AYU_144_17 PMID: 30783363
  155. Adiguna, S.P.; Panggabean, J.A.; Atikana, A.; Untari, F.; Izzati, F.; Bayu, A.; Rosyidah, A.; Rahmawati, S.I.; Putra, M.Y. Antiviral activities of andrographolide and its derivatives: Mechanism of action and delivery system. Pharmaceuticals, 2021, 14(11), 1102. doi: 10.3390/ph14111102 PMID: 34832884
  156. Yenuganti, V.R.; Afroz, S.; Khan, R.A.; Bharadwaj, C.; Nabariya, D.K.; Nayak, N.; Subbiah, M.; Chintala, K.; Banerjee, S.; Reddanna, P.; Khan, N. Milk exosomes elicit a potent anti-viral activity against dengue virus. J. Nanobiotechnol., 2022, 20(1), 317. doi: 10.1186/s12951-022-01496-5 PMID: 35794557
  157. Mahendru, G.; Sharma, P. K.; Singh, A. K.; Mondal, S. C. Role of goat milk and milk products in dengue fever. J. Pharmaceut. Biomed. Sci., 2011, 8(6), 08.
  158. Zeng, Y.; Pu, X.; Yang, J.; Du, J.; Yang, X.; Li, X.; Li, L.; Zhou, Y.; Yang, T. Preventive and therapeutic role of functional ingredients of barley grass for chronic diseases in human beings. Oxid. Med. Cell. Longev., 2018, 2018, 1-15. doi: 10.1155/2018/3232080 PMID: 29849880
  159. Bency, B.J.; Helen, P.A.M. In silico identification of dengue inhibitors in giloy (tinospora cordifolia) and papaya. Int. J. Emerg. Technol. Innov. Res., 2018, 5, 506-551.
  160. Al-Timimi, L.A.N. Antibacterial and anticancer activities of fenugreek seed extract. Asian Pac. J. Cancer Prev., 2019, 20(12), 3771-3776. doi: 10.31557/APJCP.2019.20.12.3771 PMID: 31870120
  161. Balasubramanian, A.; Pilankatta, R.; Teramoto, T.; Sajith, A.M.; Nwulia, E.; Kulkarni, A.; Padmanabhan, R. Inhibition of dengue virus by curcuminoids. Antiviral Res., 2019, 162, 71-78. doi: 10.1016/j.antiviral.2018.12.002 PMID: 30529358
  162. Anand, P.; Kunnumakkara, A.B.; Newman, R.A.; Aggarwal, B.B. Bioavailability of curcumin: Problems and promises. Mol. Pharm., 2007, 4(6), 807-818. doi: 10.1021/mp700113r PMID: 17999464
  163. Cohen, M. Tulsi - Ocimum sanctum: A herb for all reasons. J. Ayurveda Integr. Med., 2014, 5(4), 251-259. doi: 10.4103/0975-9476.146554 PMID: 25624701
  164. Lim, S.Y.M.; Chieng, J.Y.; Pan, Y. Recent insights on anti-dengue virus (DENV) medicinal plants: Review on in vitro, in vivo and in silico discoveries. All Life, 2021, 14(1), 1-33. doi: 10.1080/26895293.2020.1856192
  165. Chavda, V.P.; Patel, A.B.; Vihol, D.; Vaghasiya, D.D.; Ahmed, K.M.S.B.; Trivedi, K.U.; Dave, D.J. Herbal remedies, nutraceuticals, and dietary supplements for covid-19 management: An update. Clin. Complement. Med. Pharmacol., 2022, 2(1), 100021. doi: 10.1016/j.ccmp.2022.100021
  166. Saqallah, F.G.; Abbas, M.A.; Wahab, H.A. Recent advances in natural products as potential inhibitors of dengue virus with a special emphasis on NS2b/NS3 protease. Phytochemistry, 2022, 202, 113362. doi: 10.1016/j.phytochem.2022.113362 PMID: 35948138
  167. Nave, O.P. Modification of semi-analytical method applied system of ODE. Mod. Appl. Sci., 2020, 14(6), 75. doi: 10.5539/mas.v14n6p75

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