Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Development in the Inhibition of Dengue Proteases as Drug Targets

Author(s): Muhammad Akram, Shehryar Hameed, Abbas Hassan and Khalid Mohammed Khan*

Volume 31, Issue 16, 2024

Published on: 25 September, 2023

Page: [2195 - 2233] Pages: 39

DOI: 10.2174/0929867331666230918110144

Price: $65

Abstract

Background: Viral infections continue to increase morbidity and mortality severely. The flavivirus genus has fifty different species, including the dengue, Zika, and West Nile viruses that can infect 40% of individuals globally, who reside in at least a hundred different countries. Dengue, one of the oldest and most dangerous human infections, was initially documented by the Chinese Medical Encyclopedia in the Jin period. It was referred to as "water poison," connected to flying insects, i.e., Aedes aegypti and Aedes albopictus. DENV causes some medical expressions like dengue hemorrhagic fever, acute febrile illness, and dengue shock syndrome.

Objective: According to the World Health Organization report of 2012, 2500 million people are in danger of contracting dengue fever worldwide. According to a recent study, 96 million of the 390 million dengue infections yearly show some clinical or subclinical severity. There is no antiviral drug or vaccine to treat this severe infection. It can be controlled by getting enough rest, drinking plenty of water, and using painkillers. The first dengue vaccine created by Sanofi, called Dengvaxia, was previously approved by the USFDA in 2019. All four serotypes of the DENV1-4 have shown re-infection in vaccine recipients. However, the usage of Dengvaxia has been constrained by its adverse effects.

Conclusion: Different classes of compounds have been reported against DENV, such as nitrogen-containing heterocycles (i.e., imidazole, pyridine, triazoles quinazolines, quinoline, and indole), oxygen-containing heterocycles (i.e., coumarins), and some are mixed heterocyclic compounds of S, N (thiazole, benzothiazine, and thiazolidinediones), and N, O (i.e., oxadiazole). There have been reports of computationally designed compounds to impede the molecular functions of specific structural and non-structural proteins as potential therapeutic targets. This review summarized the current progress in developing dengue protease inhibitors.

« Previous Next »
[1]
Lancet, T. Neglected tropical diseases: becoming less neglected. Lancet, 2014, 383(9925), 1269.
[http://dx.doi.org/10.1016/S0140-6736(14)60629-2] [PMID: 24725560]
[2]
LaBeaud, A.D. Why arboviruses can be neglected tropical diseases. PLoS Negl. Trop. Dis., 2008, 2(6), e247.
[http://dx.doi.org/10.1371/journal.pntd.0000247] [PMID: 18575597]
[3]
Gubler, D.J. The global emergence/resurgence of arboviral diseases as public health problems. Arch. Med. Res., 2002, 33(4), 330-342.
[http://dx.doi.org/10.1016/S0188-4409(02)00378-8] [PMID: 12234522]
[4]
Burrows, J.N.; Elliott, R.L.; Kaneko, T.; Mowbray, C.E.; Waterson, D. The role of modern drug discovery in the fight against neglected and tropical diseases. MedChemComm, 2014, 5(6), 688-700.
[http://dx.doi.org/10.1039/c4md00011k]
[5]
Lai, P.C.; Lee, S.S.; Kao, C.H.; Chen, Y.S.; Huang, C-K.; Lin, W-R.; Wann, S-R.; Lin, H.H.; Yen, M.Y.; Liu, Y.C. Characteristics of a dengue hemorrhagic fever outbreak in 2001 in Kaohsiung. J. Microbiol. Immunol. Infect., 2004, 37(5), 266-270.
[PMID: 15497006]
[6]
Waterman, S.H.; Gubler, D.J. Dengue fever. Clin. Dermatol., 1989, 7(1), 117-122.
[http://dx.doi.org/10.1016/0738-081X(89)90034-5] [PMID: 2647259]
[7]
Gibbons, R.V.; Vaughn, D.W. Dengue: An escalating problem. BMJ, 2002, 324(7353), 1563-1566.
[http://dx.doi.org/10.1136/bmj.324.7353.1563] [PMID: 12089096]
[8]
Guzman, M.G.; Halstead, S.B.; Artsob, H.; Buchy, P.; Farrar, J.; Gubler, D.J.; Hunsperger, E.; Kroeger, A.; Margolis, H.S.; Martínez, E.; Nathan, M.B.; Pelegrino, J.L.; Simmons, C.; Yoksan, S.; Peeling, R.W. Dengue: A continuing global threat. Nat. Rev. Microbiol., 2010, 8(S12)(Suppl.), S7-S16.
[http://dx.doi.org/10.1038/nrmicro2460] [PMID: 21079655]
[9]
Pujar, G.V.; Sethu, A.K.; Bhagyalalitha, M.; Singh, M. Dengue structural proteins as antiviral drug targets: Current status in the drug discovery & development. Eur. J. Med. Chem., 2021, 221, 113527.
[http://dx.doi.org/10.1016/j.ejmech.2021.113527] [PMID: 34020338]
[10]
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.
[http://dx.doi.org/10.1007/s00018-010-0357-z] [PMID: 20372965]
[11]
Noble, C.G.; Shi, P.Y. Structural biology of dengue virus enzymes: Towards rational design of therapeutics. Antiviral Res., 2012, 96(2), 115-126.
[http://dx.doi.org/10.1016/j.antiviral.2012.09.007] [PMID: 22995600]
[12]
Santiago, G.A.; Vergne, E.; Quiles, Y.; Cosme, J.; Vazquez, J.; Medina, J.F.; Medina, F.; Colón, C.; Margolis, H.; Muñoz-Jordán, J.L. Analytical and clinical performance of the CDC real time RT-PCR assay for detection and typing of dengue virus. PLoS Negl. Trop. Dis., 2013, 7(7), e2311.
[http://dx.doi.org/10.1371/journal.pntd.0002311] [PMID: 23875046]
[13]
Beatty, M.E.; Margolis, H.S.; Coudeville, L.; Hutubessy, R.; Hombach, J.; Dessis, D.; Dervaux, B.; Wichmann, O.; Meltzer, M.I.; Kuritsky, J.N.; Shepard, D.S.; Beutels, P. Health economics of dengue: A systematic literature review and expert panel’s assessment. Am. J. Trop. Med. Hyg., 2011, 84(3), 473-488.
[http://dx.doi.org/10.4269/ajtmh.2011.10-0521] [PMID: 21363989]
[14]
Alvarez, M.; Morier, L.; Bernardo, L.; Halstead, S.B.; Guzman, M.G.; Castro, O.; Vázquez, S.; Gonzalez, D.; Rodriguez-Roche, R.; Kouri, G. Dengue hemorrhagic fever caused by sequential dengue 1-3 virus infections over a long time interval: Havana epidemic, 2001-2002. Am. J. Trop. Med. Hyg., 2006, 75(6), 1113-1117.
[http://dx.doi.org/10.4269/ajtmh.2006.75.1113] [PMID: 17172378]
[15]
Halstead, S.B. Neutralization and antibody-dependent enhancement of dengue viruses. Adv. Virus Res., 2003, 60, 421-467.
[http://dx.doi.org/10.1016/S0065-3527(03)60011-4] [PMID: 14689700]
[16]
Kamasa-Quashie, D. Relationship between single nucleotide polymorphisms and severe dengue in a Brazilian population; University of Pittsburgh, 2020.
[17]
Simmons, C.P.; McPherson, K.; Van Vinh Chau, N.; Hoai Tam, D.T.; Young, P.; Mackenzie, J.; Wills, B. Recent advances in dengue pathogenesis and clinical management. Vaccine, 2015, 33(50), 7061-7068.
[http://dx.doi.org/10.1016/j.vaccine.2015.09.103]
[18]
Organization, W.H. Dengue vaccine: WHO position paper – July 2016. Wkly. Epidemiol. Rec., 2016, 91(30), 349-364.
[PMID: 27476189]
[19]
Otto, H.H.; Schirmeister, T. Cysteine proteases and their inhibitors. Chem. Rev., 1997, 97(1), 133-172.
[http://dx.doi.org/10.1021/cr950025u] [PMID: 11848867]
[20]
Vasiljeva, O.; Reinheckel, T.; Peters, C.; Turk, D.; Turk, V.; Turk, B. Emerging roles of cysteine cathepsins in disease and their potential as drug targets. Curr. Pharm. Des., 2007, 13(4), 387-403.
[http://dx.doi.org/10.2174/138161207780162962] [PMID: 17311556]
[21]
Walsh, G. Proteins: Biochemistry and Biotechnology; John Wiley & Sons, 2015.
[22]
McGrath, M.E. The lysosomal cysteine proteases. Annu. Rev. Biophys. Biomol. Struct., 1999, 28(1), 181-204.
[http://dx.doi.org/10.1146/annurev.biophys.28.1.181] [PMID: 10410800]
[23]
Petrov, V.; Fagard, R.; Lijnen, P. Effect of protease inhibitors on angiotensin-converting enzyme activity in human T-lymphocytes. Am. J. Hypertens., 2000, 13(5), 535-539.
[http://dx.doi.org/10.1016/S0895-7061(99)00236-8] [PMID: 10826406]
[24]
Hirai, T.; Kanda, T.; Sato, K.; Takaishi, M.; Nakajima, K.; Yamamoto, M.; Kamijima, R.; DiGiovanni, J.; Sano, S. Cathepsin K is involved in development of psoriasis-like skin lesions through TLR-dependent Th17 activation. J. Immunol., 2013, 190(9), 4805-4811.
[http://dx.doi.org/10.4049/jimmunol.1200901] [PMID: 23543761]
[25]
Sajid, M.; McKerrow, J.H. Cysteine proteases of parasitic organisms. Mol. Biochem. Parasitol., 2002, 120(1), 1-21.
[http://dx.doi.org/10.1016/S0166-6851(01)00438-8] [PMID: 11849701]
[26]
Chambers, T.J.; Hahn, C.S.; Galler, R.; Rice, C.M. Flavivirus genome organization, expression, and replication. Annu. Rev. Microbiol., 1990, 44(1), 649-688.
[http://dx.doi.org/10.1146/annurev.mi.44.100190.003245] [PMID: 2174669]
[27]
Clyde, K.; Kyle, J.L.; Harris, E. Recent advances in deciphering viral and host determinants of dengue virus replication and pathogenesis. J. Virol., 2006, 80(23), 11418-11431.
[http://dx.doi.org/10.1128/JVI.01257-06] [PMID: 16928749]
[28]
Stadler, K.; Allison, S.L.; Schalich, J.; Heinz, F.X. Proteolytic activation of tick-borne encephalitis virus by furin. J. Virol., 1997, 71(11), 8475-8481.
[http://dx.doi.org/10.1128/jvi.71.11.8475-8481.1997] [PMID: 9343204]
[29]
Fahimi, H.; Mohammadipour, M.; Haddad Kashani, H.; Parvini, F.; Sadeghizadeh, M. Dengue viruses and promising envelope protein domain III-based vaccines. Appl. Microbiol. Biotechnol., 2018, 102(7), 2977-2996.
[http://dx.doi.org/10.1007/s00253-018-8822-y] [PMID: 29470620]
[30]
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.
[http://dx.doi.org/10.1038/nature02165] [PMID: 14737159]
[31]
Byk, L.A.; Gamarnik, A.V. Properties and functions of the dengue virus capsid protein. Annu. Rev. Virol., 2016, 3(1), 263-281.
[http://dx.doi.org/10.1146/annurev-virology-110615-042334] [PMID: 27501261]
[32]
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.
[http://dx.doi.org/10.1016/j.antiviral.2018.04.019] [PMID: 29709563]
[33]
Yeo, A.S.L.; Rathakrishnan, A.; Wang, S.M.; Ponnampalavanar, S.; Manikam, R.; Sathar, J.; Kumari Natkunam, S.; Sekaran, S.D. Dengue patients exhibit higher levels of PrM and E antibodies than their asymptomatic counterparts. BioMed Res. Int., 2015, 2015, 1-10.
[34]
Hsieh, S.C.; Wu, Y.C.; Zou, G.; Nerurkar, V.R.; Shi, P.Y.; Wang, W.K. Highly conserved residues in the helical domain of dengue virus type 1 precursor membrane protein are involved in assembly, precursor membrane (prM) protein cleavage, and entry. J. Biol. Chem., 2014, 289(48), 33149-33160.
[http://dx.doi.org/10.1074/jbc.M114.610428] [PMID: 25326389]
[35]
Navarro-Sanchez, E.; Altmeyer, R.; Amara, A.; Schwartz, O.; Fieschi, F.; Virelizier, J.L.; Arenzana-Seisdedos, F.; Desprès, P. Dendritic-cell-specific ICAM3-grabbing nonintegrin is essential for the productive infection of human dendritic cells by mosquito‐cell-derived dengue viruses. EMBO Rep., 2003, 4(7), 723-728.
[http://dx.doi.org/10.1038/sj.embor.embor866] [PMID: 12783086]
[36]
Noble, C.G.; Chen, Y.L.; Dong, H.; Gu, F.; Lim, S.P.; Schul, W.; Wang, Q.Y.; Shi, P.Y. Strategies for development of dengue virus inhibitors. Antiviral Res., 2010, 85(3), 450-462.
[http://dx.doi.org/10.1016/j.antiviral.2009.12.011] [PMID: 20060421]
[37]
Mukhopadhyay, S.; Kuhn, R.J.; Rossmann, M.G. A structural perspective of the flavivirus life cycle. Nat. Rev. Microbiol., 2005, 3(1), 13-22.
[http://dx.doi.org/10.1038/nrmicro1067] [PMID: 15608696]
[38]
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.
[http://dx.doi.org/10.1128/AAC.01148-08] [PMID: 19223625]
[39]
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.
[http://dx.doi.org/10.1016/j.antiviral.2009.09.011] [PMID: 19800368]
[40]
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.
[http://dx.doi.org/10.1021/cb800176t] [PMID: 19053243]
[41]
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.
[http://dx.doi.org/10.1016/j.antiviral.2009.09.007] [PMID: 19781577]
[42]
Schmidt, A.G.; Lee, K.; Yang, P.L.; Harrison, S.C. Correction: Small-molecule inhibitors of dengue-virus entry. PLoS Pathog., 2019, 15(1), e1007553.
[http://dx.doi.org/10.1371/journal.ppat.1007553] [PMID: 30703168]
[43]
Costin, J.M.; Jenwitheesuk, E.; Lok, S.M.; Hunsperger, E.; Conrads, K.A.; Fontaine, K.A.; Rees, C.R.; Rossmann, M.G.; Isern, S.; Samudrala, R.; Michael, S.F. Structural optimization and de novo design of dengue virus entry inhibitory peptides. PLoS Negl. Trop. Dis., 2010, 4(6), e721.
[http://dx.doi.org/10.1371/journal.pntd.0000721] [PMID: 20582308]
[44]
Hrobowski, Y.M.; Garry, R.F.; Michael, S.F. The involvement of survival signaling pathways in rubella-virus induced apoptosis. Virol. J., 2005, 2(1), 1-10.
[http://dx.doi.org/10.1186/1743-422X-2-1]
[45]
Modis, Y.; Ogata, S.; Clements, D.; Harrison, S.C. A ligand-binding pocket in the dengue virus envelope glycoprotein. Proc. Natl. Acad. Sci. USA, 2003, 100(12), 6986-6991.
[http://dx.doi.org/10.1073/pnas.0832193100] [PMID: 12759475]
[46]
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.
[http://dx.doi.org/10.1016/j.antiviral.2013.09.013] [PMID: 24076358]
[47]
Alhoot, M.A.; Rathinam, A.K.; Wang, S.M.; Manikam, R.; Sekaran, S.D. Inhibition of dengue virus entry into target cells using synthetic antiviral peptides. Int. J. Med. Sci., 2013, 10(6), 719-729.
[http://dx.doi.org/10.7150/ijms.5037] [PMID: 23630436]
[48]
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.
[http://dx.doi.org/10.1016/j.bmcl.2015.02.059] [PMID: 25791449]
[49]
Lin, C.; Yu, J.; Hussain, M.; Zhou, Y.; Duan, A.; Pan, W.; Yuan, J.; Zhang, J. Design, synthesis, and biological evaluation of novel 7-deazapurine nucleoside derivatives as potential anti-dengue virus agents. Antiviral Res., 2018, 149, 95-105.
[http://dx.doi.org/10.1016/j.antiviral.2017.11.005] [PMID: 29129706]
[50]
Samsa, M.M.; Mondotte, J.A.; Iglesias, N.G.; Assunção-Miranda, I.; Barbosa-Lima, G.; Da Poian, A.T.; Bozza, P.T.; Gamarnik, A.V. Dengue virus capsid protein usurps lipid droplets for viral particle formation. PLoS Pathog., 2009, 5(10), e1000632.
[http://dx.doi.org/10.1371/journal.ppat.1000632] [PMID: 19851456]
[51]
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.
[http://dx.doi.org/10.1128/AAC.01429-12] [PMID: 23070172]
[52]
Lee, J.C.; Tseng, C.K.; Wu, Y.H.; Kaushik-Basu, N.; Lin, C.K.; Chen, W.C.; Wu, H.N. Characterization of the activity of 2′-C-methylcytidine against dengue virus replication. Antiviral Res., 2015, 116, 1-9.
[http://dx.doi.org/10.1016/j.antiviral.2015.01.002] [PMID: 25614455]
[53]
Peng, M.; Watanabe, S.; Chan, K.W.K.; He, Q.; Zhao, Y.; Zhang, Z.; Lai, X.; Luo, D.; Vasudevan, S.G.; Li, G. Luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin. Antiviral Res., 2017, 143, 176-185.
[http://dx.doi.org/10.1016/j.antiviral.2017.03.026] [PMID: 28389141]
[54]
Alayli, F.; Scholle, F. Dengue virus NS1 enhances viral replication and pro-inflammatory cytokine production in human dendritic cells. Virology, 2016, 496, 227-236.
[http://dx.doi.org/10.1016/j.virol.2016.06.008]
[55]
Lindenbach, B.D.; Rice, C.M. Genetic interaction of flavivirus nonstructural proteins NS1 and NS4A as a determinant of replicase function. J. Virol., 1999, 73(6), 4611-4621.
[http://dx.doi.org/10.1128/JVI.73.6.4611-4621.1999] [PMID: 10233920]
[56]
Konishi, E.; Kosugi, S.; Imoto, J. Dengue tetravalent DNA vaccine inducing neutralizing antibody and anamnestic responses to four serotypes in mice. Vaccine, 2006, 24(12), 2200-2207.
[http://dx.doi.org/10.1016/j.vaccine.2005.11.002]
[57]
Kurane, I.; Brinton, M.A.; Samson, A.L.; Ennis, F.A. Dengue virus-specific, human CD4+ CD8- cytotoxic T-cell clones: Multiple patterns of virus cross-reactivity recognized by NS3-specific T-cell clones. J. Virol., 1991, 65(4), 1823-1828.
[http://dx.doi.org/10.1128/jvi.65.4.1823-1828.1991] [PMID: 1705990]
[58]
Porter, K.R.; Raviprakash, K. Nucleic acid (DNA) immunization as a platform for dengue vaccine development. Vaccine, 2015, 33(50), 7135-7140.
[http://dx.doi.org/10.1016/j.vaccine.2015.09.102]
[59]
Rothan, H.A.; Bahrani, H.; Rahman, N.; Yusof, R. Identification of natural antimicrobial agents to treat dengue infection: In vitro analysis of latarcin peptide activity against dengue virus. BMC Microbiol., 2014, 14(1), 140.
[http://dx.doi.org/10.1186/1471-2180-14-140]
[60]
Jacob, G.S. Glycosylation inhibitors in biology and medicine. Curr. Opin. Struct. Biol., 1995, 5(5), 605-611.
[http://dx.doi.org/10.1016/0959-440X(95)80051-4] [PMID: 8574695]
[61]
Elbein, A.D. Glycosidase inhibitors: inhibitors of N‐linked oligosaccharide processing. FASEB J., 1991, 5(15), 3055-3063.
[http://dx.doi.org/10.1096/fasebj.5.15.1743438] [PMID: 1743438]
[62]
Pan, Y.T.; Hori, H.; Saul, R.; Sanford, B.A.; Molyneux, R.J.; Elbein, A.D. Castanospermine inhibits the processing of the oligosaccharide portion of the influenza viral hemagglutinin. Biochemistry, 1983, 22(16), 3975-3984.
[http://dx.doi.org/10.1021/bi00285a038]
[63]
Block, T.M.; Lu, X.; Mehta, A.S.; Blumberg, B.S.; Tennant, B.; Ebling, M.; Korba, B.; Lansky, D.M.; Jacob, G.S.; Dwek, R.A. Treatment of chronic hepadnavirus infection in a woodchuck animal model with an inhibitor of protein folding and trafficking. Nat. Med., 1998, 4(5), 610-614.
[http://dx.doi.org/10.1038/nm0598-610] [PMID: 9585237]
[64]
Courageot, M.P.; Frenkiel, M.P.; Duarte Dos Santos, C.; Deubel, V.; Desprès, P. Alpha-glucosidase inhibitors reduce dengue virus production by affecting the initial steps of virion morphogenesis in the endoplasmic reticulum. J. Virol., 2000, 74(1), 564-572.
[http://dx.doi.org/10.1128/JVI.74.1.564-572.2000] [PMID: 10590151]
[65]
Schul, W.; Liu, W.; Xu, H.Y.; Flamand, M.; Vasudevan, S.G. A dengue fever viremia model in mice shows reduction in viral replication and suppression of the inflammatory response after treatment with antiviral drugs. J. Infect. Dis., 2007, 195(5), 665-674.
[http://dx.doi.org/10.1086/511310] [PMID: 17262707]
[66]
Tan, A.; van den Broek, L.; van Boeckel, S.; Ploegh, H.; Bolscher, J. Chemical modification of the glucosidase inhibitor 1-deoxynojirimycin. Structure-activity relationships. J. Biol. Chem., 1991, 266(22), 14504-14510.
[http://dx.doi.org/10.1016/S0021-9258(18)98715-6] [PMID: 1650361]
[67]
Mellor, H.R.; Nolan, J.; Pickering, L.; Wormald, M.R.; Platt, F.M.; Dwek, R.A.; Fleet, G.W.J.; Butters, T.D. Preparation, biochemical characterization and biological properties of radiolabelled N-alkylated deoxynojirimycins. Biochem. J., 2002, 366(1), 225-233.
[http://dx.doi.org/10.1042/bj20020466] [PMID: 11982484]
[68]
Rathore, A.P.S.; Paradkar, P.N.; Watanabe, S.; Tan, K.H.; Sung, C.; Connolly, J.E.; Low, J.; Ooi, E.E.; Vasudevan, S.G. Celgosivir treatment misfolds dengue virus NS1 protein, induces cellular pro-survival genes and protects against lethal challenge mouse model. Antiviral Res., 2011, 92(3), 453-460.
[http://dx.doi.org/10.1016/j.antiviral.2011.10.002] [PMID: 22020302]
[69]
Raut, R.; Beesetti, H.; Tyagi, P.; Khanna, I.; Jain, S.K.; Jeankumar, V.U.; Yogeeswari, P.; Sriram, D.; Swaminathan, S. Complete genome sequencing and phylogenetic analysis of dengue type 1 virus isolated from Jeddah, Saudi Arabia. J. Virol., 2015, 12(1), 1-7.
[http://dx.doi.org/10.1186/s12985-014-0235-7]
[70]
Xie, X.; Zou, J.; Zhang, X.; Zhou, Y.; Routh, A.L.; Kang, C.; Popov, V.L.; Chen, X.; Wang, Q-Y.; Dong, H. Dengue NS2A protein orchestrates virus assembly. Cell Host Microb.,, 2019, 26(5), 606-622.
[71]
Nemésio, H.; Villalaín, J. Membrane interacting regions of Dengue virus NS2A protein. J. Phys. Chem. B, 2014, 118(34), 10142-10155.
[http://dx.doi.org/10.1021/jp504911r] [PMID: 25119664]
[72]
Li, Y.; Li, Q.; Wong, Y.L.; Liew, L.S.Y.; Kang, C. Membrane topology of NS2B of dengue virus revealed by NMR spectroscopy. Biochim. Biophys. Acta Biomembr., 2015, 1848(10), 2244-2252.
[http://dx.doi.org/10.1016/j.bbamem.2015.06.010]
[73]
Kim, Y.M.; Gayen, S.; Kang, C.; Joy, J.; Huang, Q.; Chen, A.S.; Wee, J.L.K.; Ang, M.J.Y.; Lim, H.A.; Hung, A.W.; Li, R.; Noble, C.G.; Lee, L.T.; Yip, A.; Wang, Q.Y.; Chia, C.S.B.; Hill, J.; Shi, P.Y.; Keller, T.H. NMR analysis of a novel enzymatically active unlinked dengue NS2B-NS3 protease complex. J. Biol. Chem., 2013, 288(18), 12891-12900.
[http://dx.doi.org/10.1074/jbc.M112.442723] [PMID: 23511634]
[74]
Hariono, M.; Choi, S.B.; Roslim, R.F.; Nawi, M.S.; Tan, M.L.; Kamarulzaman, E.E.; Mohamed, N.; Yusof, R.; Othman, S.; Abd Rahman, N.; Othman, R.; Wahab, H.A. Thioguanine-based DENV-2 NS2B/NS3 protease inhibitors: Virtual screening, synthesis, biological evaluation and molecular modelling. PLoS One, 2019, 14(1), e0210869.
[http://dx.doi.org/10.1371/journal.pone.0210869] [PMID: 30677071]
[75]
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(1), 229-238.
[http://dx.doi.org/10.1128/AAC.00855-10] [PMID: 20937790]
[76]
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.
[http://dx.doi.org/10.1016/j.bioorg.2015.07.005] [PMID: 26247308]
[77]
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.
[http://dx.doi.org/10.1038/aps.2015.56] [PMID: 26279156]
[78]
Osman, H.; Idris, N.H.; Kamarulzaman, E.E.; Wahab, H.A.; Hassan, M.Z. 3,5-Bis(arylidene)-4-piperidones as potential dengue protease inhibitors. Acta Pharm. Sin. B, 2017, 7(4), 479-484.
[http://dx.doi.org/10.1016/j.apsb.2017.04.009] [PMID: 28752033]
[79]
Weng, Z.; Shao, X.; Graf, D.; Wang, C.; Klein, C.D.; Wang, J.; Zhou, G.C. Identification of fused bicyclic derivatives of pyrrolidine and imidazolidinone as dengue virus-2 NS2B-NS3 protease inhibitors. Eur. J. Med. Chem., 2017, 125, 751-759.
[http://dx.doi.org/10.1016/j.ejmech.2016.09.063] [PMID: 27721158]
[80]
Hamdani, S.S.; Khan, B.A.; Hameed, S.; Batool, F.; Saleem, H.N.; Mughal, E.U.; Saeed, M. Synthesis and evaluation of novel S-benzyl- and S-alkylphthalimide-oxadiazole-benzenesulfonamide hybrids as inhibitors of dengue virus protease. Bioorg. Chem., 2020, 96, 103567.
[http://dx.doi.org/10.1016/j.bioorg.2020.103567] [PMID: 32062063]
[81]
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.
[http://dx.doi.org/10.1016/j.bmc.2011.05.015] [PMID: 21641807]
[82]
Lai, H.; Dou, D.; Aravapalli, S.; Teramoto, T.; Lushington, G.H.; Mwania, T.M.; Alliston, K.R.; Eichhorn, D.M.; Padmanabhan, R.; Groutas, W.C. Design, synthesis and characterization of novel 1,2-benzisothiazol-3(2H)-one and 1,3,4-oxadiazole hybrid derivatives: Potent inhibitors of Dengue and West Nile virus NS2B/NS3 proteases. Bioorg. Med. Chem., 2013, 21(1), 102-113.
[http://dx.doi.org/10.1016/j.bmc.2012.10.058] [PMID: 23211969]
[83]
Lai, H.; Sridhar Prasad, G.; Padmanabhan, R. Characterization of 8-hydroxyquinoline derivatives containing aminobenzothiazole as inhibitors of dengue virus type 2 protease in vitro. Antiviral Res., 2013, 97(1), 74-80.
[http://dx.doi.org/10.1016/j.antiviral.2012.10.009] [PMID: 23127365]
[84]
Behnam, M.A.M.; Graf, D.; Bartenschlager, R.; Zlotos, D.P.; Klein, C.D. Discovery of nanomolar dengue and west nile virus protease inhibitors containing a 4-benzyloxyphenylglycine residue. J. Med. Chem., 2015, 58(23), 9354-9370.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01441] [PMID: 26562070]
[85]
Nitsche, C.; Schreier, V.N.; Behnam, M.A.M.; Kumar, A.; Bartenschlager, R.; Klein, C.D. Thiazolidinone-peptide hybrids as dengue virus protease inhibitors with antiviral activity in cell culture. J. Med. Chem., 2013, 56(21), 8389-8403.
[http://dx.doi.org/10.1021/jm400828u] [PMID: 24083834]
[86]
Liu, H.; Wu, R.; Sun, Y.; Ye, Y.; Chen, J.; Luo, X.; Shen, X.; Liu, H. Identification of novel thiadiazoloacrylamide analogues as inhibitors of dengue-2 virus NS2B/NS3 protease. Bioorg. Med. Chem., 2014, 22(22), 6344-6352.
[http://dx.doi.org/10.1016/j.bmc.2014.09.057] [PMID: 25438757]
[87]
Gao, Y.; Cui, T.; Lam, Y. Synthesis and disulfide bond connectivity–activity studies of a kalata B1-inspired cyclopeptide against dengue NS2B–NS3 protease. Bioorg. Med. Chem., 2010, 18(3), 1331-1336.
[http://dx.doi.org/10.1016/j.bmc.2009.12.026] [PMID: 20042339]
[88]
Prusis, P.; Junaid, M.; Petrovska, R.; Yahorava, S.; Yahorau, A.; Katzenmeier, G.; Lapins, M.; Wikberg, J.E.S. Design and evaluation of substrate-based octapeptide and non substrate-based tetrapeptide inhibitors of dengue virus NS2B–NS3 proteases. Biochem. Biophys. Res. Commun., 2013, 434(4), 767-772.
[http://dx.doi.org/10.1016/j.bbrc.2013.03.139] [PMID: 23587903]
[89]
Weigel, L.F.; Nitsche, C.; Graf, D.; Bartenschlager, R.; Klein, C.D. Phenylalanine and phenylglycine analogues as arginine mimetics in dengue protease inhibitors. J. Med. Chem., 2015, 58(19), 7719-7733.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00612] [PMID: 26367391]
[90]
Arias, C.F.; Preugschat, F.; Strauss, J.H. Dengue 2 virus NS2B and NS3 form a stable complex that can cleave NS3 within the helicase domain. Virology, 1993, 193(2), 888-899.
[http://dx.doi.org/10.1006/viro.1993.1198]
[91]
Falgout, B.; Pethel, M.; Zhang, Y.M.; Lai, C.J. Both nonstructural proteins NS2B and NS3 are required for the proteolytic processing of dengue virus nonstructural proteins. J. Virol., 1991, 65(5), 2467-2475.
[http://dx.doi.org/10.1128/jvi.65.5.2467-2475.1991] [PMID: 2016768]
[92]
Falgout, B.; Miller, R.H.; Lai, C.J. Deletion analysis of dengue virus type 4 nonstructural protein NS2B: Identification of a domain required for NS2B-NS3 protease activity. J. Virol., 1993, 67(4), 2034-2042.
[http://dx.doi.org/10.1128/jvi.67.4.2034-2042.1993] [PMID: 8383225]
[93]
Li, H.; Clum, S.; You, S.; Ebner, K.E.; Padmanabhan, R. The serine protease and RNA-stimulated nucleoside triphosphatase and RNA helicase functional domains of dengue virus type 2 NS3 converge within a region of 20 amino acids. J. Virol., 1999, 73(4), 3108-3116.
[http://dx.doi.org/10.1128/JVI.73.4.3108-3116.1999] [PMID: 10074162]
[94]
Yusof, R.; Clum, S.; Wetzel, M.; Murthy, H.M.K.; Padmanabhan, R. Purified NS2B/NS3 serine protease of dengue virus type 2 exhibits cofactor NS2B dependence for cleavage of substrates with dibasic amino acids in vitro. J. Biol. Chem., 2000, 275(14), 9963-9969.
[http://dx.doi.org/10.1074/jbc.275.14.9963] [PMID: 10744671]
[95]
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(49), 45762-45771.
[http://dx.doi.org/10.1074/jbc.M107360200] [PMID: 11581268]
[96]
Li, J.; Lim, S.P.; Beer, D.; Patel, V.; Wen, D.; Tumanut, C.; Tully, D.C.; Williams, J.A.; Jiricek, J.; Priestle, J.P.; Harris, J.L.; Vasudevan, S.G. Functional profiling of recombinant NS3 proteases from all four serotypes of dengue virus using tetrapeptide and octapeptide substrate libraries. J. Biol. Chem., 2005, 280(31), 28766-28774.
[http://dx.doi.org/10.1074/jbc.M500588200] [PMID: 15932883]
[97]
Murthy, H.M.K.; Clum, S.; Padmanabhan, R. Dengue virus NS3 serine protease. Crystal structure and insights into interaction of the active site with substrates by molecular modeling and structural analysis of mutational effects. J. Biol. Chem., 1999, 274(9), 5573-5580.
[http://dx.doi.org/10.1074/jbc.274.9.5573] [PMID: 10026173]
[98]
Hsu, J.; Wang, H.C.; Chen, G.W.; Shih, S.R. Antiviral drug discovery targeting to viral proteases. Curr. Pharm. Des., 2006, 12(11), 1301-1314.
[http://dx.doi.org/10.2174/138161206776361110] [PMID: 16611117]
[99]
Menéndez-Arias, L. Molecular basis of human immunodeficiency virus drug resistance: An update. Antiviral Res., 2010, 85(1), 210-231.
[http://dx.doi.org/10.1016/j.antiviral.2009.07.006] [PMID: 19616029]
[100]
Wendt, A.; Adhoute, X.; Castellani, P.; Oules, V.; Ansaldi, C.; Benali, S.; Bourlière, M. Chronic hepatitis C: Future treatment. Clin. Pharmacol., 2014, 6, 1-17.
[101]
Natarajan, S. NS3 protease from flavivirus as a target for designing antiviral inhibitors against dengue virus. Genet. Mol. Biol., 2010, 33(2), 214-219.
[http://dx.doi.org/10.1590/S1415-47572010000200002] [PMID: 21637471]
[102]
Bazan, J.F.; Fletterick, R.J. Detection of a trypsin-like serine protease domain in flaviviruses and pestviruses. Virology, 1989, 171(2), 637-639.
[http://dx.doi.org/10.1016/0042-6822(89)90639-9]
[103]
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(4), 372-373.
[http://dx.doi.org/10.1038/nsmb1073] [PMID: 16532006]
[104]
Mueller, N.H.; Pattabiraman, N.; Ansarah-Sobrinho, C.; Viswanathan, P.; Pierson, T.C.; Padmanabhan, R. Identification and biochemical characterization of small-molecule inhibitors of west nile virus serine protease by a high-throughput screen. Antimicrob. Agents Chemother., 2008, 52(9), 3385-3393.
[http://dx.doi.org/10.1128/AAC.01508-07] [PMID: 18606844]
[105]
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.
[http://dx.doi.org/10.1016/j.antiviral.2015.04.010] [PMID: 25912817]
[106]
Xie, X.; Zou, J.; Wang, Q.Y.; Shi, P.Y. Targeting dengue virus NS4B protein for drug discovery. Antiviral Res., 2015, 118, 39-45.
[http://dx.doi.org/10.1016/j.antiviral.2015.03.007] [PMID: 25796970]
[107]
Lee, J.C.; Chang, F.R.; Chen, S.R.; Wu, Y.H.; Hu, H.C.; Wu, Y.C.; Backlund, A.; Cheng, Y.B. Anti-dengue virus constituents from formosan zoanthid palythoa mutuki. Mar. Drugs, 2016, 14(8), 151.
[http://dx.doi.org/10.3390/md14080151] [PMID: 27517937]
[108]
Naik, N.G.; Wu, H.N. Mutation of putative N-glycosylation sites on dengue virus NS4B decreases RNA replication. J. Virol., 2015, 89(13), 6746-6760.
[http://dx.doi.org/10.1128/JVI.00423-15] [PMID: 25878113]
[109]
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.
[http://dx.doi.org/10.1128/AAC.03543-14] [PMID: 25487800]
[110]
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.
[http://dx.doi.org/10.1128/AAC.01281-13] [PMID: 24145533]
[111]
Balasubramanian, A.; Manzano, M.; Teramoto, T.; Pilankatta, R.; Padmanabhan, R. High-throughput screening for the identification of small-molecule inhibitors of the flaviviral protease. Antiviral Res., 2016, 134, 6-16.
[http://dx.doi.org/10.1016/j.antiviral.2016.08.014] [PMID: 27539384]
[112]
Gan, C.S.; Lee, Y.K.; Heh, C.H.; Rahman, N.A.; Yusof, R.; Othman, S. The synthetic molecules YK51 and YK73 attenuate replication of dengue virus serotype 2. Trop. Biomed., 2017, 34(2), 270-283.
[PMID: 33593007]
[113]
Padmapriya, P.; Gracy Fathima, S.; Ramanathan, G. v, Y.; A, K.S.; Kaveri, K.; Gunasekaran, P.; Tirichurapalli Sivagnanam, U.; Thennarasu, S. Development of antiviral inhibitor against dengue 2 targeting Ns3 protein: In vitro and in silico significant studies. Acta Trop., 2018, 188, 1-8.
[http://dx.doi.org/10.1016/j.actatropica.2018.08.022] [PMID: 30145258]
[114]
Li, L.; Basavannacharya, C.; Chan, K.W.K.; Shang, L.; Vasudevan, S.G.; Yin, Z. Structure-guided discovery of a novel non-peptide inhibitor of dengue virus NS2B-NS3 protease. Eur. J. Med. Chem., 2015, 86, 255-264.
[115]
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.
[http://dx.doi.org/10.1080/14756366.2017.1355791] [PMID: 28776445]
[116]
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.
[http://dx.doi.org/10.1074/jbc.M609919200] [PMID: 17276984]
[117]
Li, Y.; Lee, M.Y.; Loh, Y.R.; Kang, C. Secondary structure and membrane topology of dengue virus NS4A protein in micelles. Biochim. Biophys. Acta Biomembr., 2018, 1860(2), 442-450.
[http://dx.doi.org/10.1016/j.bbamem.2017.10.016] [PMID: 29055659]
[118]
Hung, Y.F.; Schwarten, M.; Hoffmann, S.; Willbold, D.; Sklan, E.; Koenig, B. Amino terminal region of dengue virus NS4A cytosolic domain binds to highly curved liposomes. Viruses, 2015, 7(7), 4119-4130.
[http://dx.doi.org/10.3390/v7072812]
[119]
Stern, O.; Hung, Y.F.; Valdau, O.; Yaffe, Y.; Harris, E.; Hoffmann, S.; Willbold, D.; Sklan, E.H. An N-terminal amphipathic helix in dengue virus nonstructural protein 4A mediates oligomerization and is essential for replication. J. Virol., 2013, 87(7), 4080-4085.
[http://dx.doi.org/10.1128/JVI.01900-12] [PMID: 23325687]
[120]
Lee, C.M.; Xie, X.; Zou, J.; Li, S.H.; Lee, M.Y.Q.; Dong, H.; Qin, C.F.; Kang, C.; Shi, P.Y. Determinants of dengue virus NS4A protein oligomerization. J. Virol., 2015, 89(12), 6171-6183.
[http://dx.doi.org/10.1128/JVI.00546-15] [PMID: 25833044]
[121]
Zou, J.; Xie, X.; Wang, Q.Y.; Dong, H.; Lee, M.Y.; Kang, C.; Yuan, Z.; Shi, P.Y. Characterization of dengue virus NS4A and NS4B protein interaction. J. Virol., 2015, 89(7), 3455-3470.
[http://dx.doi.org/10.1128/JVI.03453-14] [PMID: 25568208]
[122]
Lin, C.; Amberg, S.M.; Chambers, T.J.; Rice, C.M. Cleavage at a novel site in the NS4A region by the yellow fever virus NS2B-3 proteinase is a prerequisite for processing at the downstream 4A/4B signalase site. J. Virol., 1993, 67(4), 2327-2335.
[http://dx.doi.org/10.1128/jvi.67.4.2327-2335.1993] [PMID: 8445732]
[123]
Reddy, S.B.G.; Chin, W-X.; Shivananju, N.S. Dengue virus NS2 and NS4: Minor proteins, mammoth roles. Biochem. Pharmacol., 2018, 154, 54-63.
[http://dx.doi.org/10.1016/j.bcp.2018.04.008] [PMID: 29674002]
[124]
Ambrose, R.L.; Mackenzie, J.M. A conserved peptide in West Nile virus NS4A protein contributes to proteolytic processing and is essential for replication. J. Virol., 2011, 85(21), 11274-11282.
[http://dx.doi.org/10.1128/JVI.05864-11] [PMID: 21880777]
[125]
Wu, J.; Bera, A.K.; Kuhn, R.J.; Smith, J.L. Structure of the flavivirus helicase: Implications for catalytic activity, protein interactions, and proteolytic processing. J. Virol., 2005, 79(16), 10268-10277.
[http://dx.doi.org/10.1128/JVI.79.16.10268-10277.2005] [PMID: 16051820]
[126]
Yamashita, T.; Unno, H.; Mori, Y.; Tani, H.; Moriishi, K.; Takamizawa, A.; Agoh, M.; Tsukihara, T.; Matsuura, Y. Crystal structure of the catalytic domain of Japanese encephalitis virus NS3 helicase/nucleoside triphosphatase at a resolution of 1.8 Å. Virology, 2008, 373(2), 426-436.
[http://dx.doi.org/10.1016/j.virol.2007.12.018]
[127]
Nobori, H.; Toba, S.; Yoshida, R.; Hall, W.W.; Orba, Y.; Sawa, H.; Sato, A. Identification of compound-B, a novel anti-dengue virus agent targeting the non-structural protein 4A. Antiviral Res., 2018, 155, 60-66.
[http://dx.doi.org/10.1016/j.antiviral.2018.05.003] [PMID: 29758236]
[128]
Miller, S.; Sparacio, S.; Bartenschlager, R. Subcellular localization and membrane topology of the dengue virus type 2 non-structural protein 4B. J. Biol. Chem., 2006, 281(13), 8854-8863.
[http://dx.doi.org/10.1074/jbc.M512697200] [PMID: 16436383]
[129]
Li, Y.; Wong, Y.L.; Lee, M.Y.; Li, Q.; Wang, Q.Y.; Lescar, J.; Shi, P.Y.; Kang, C. Secondary structure and membrane topology of the full-length dengue virus NS4B in micelles. Angew. Chem., 2016, 128(39), 12247-12251.
[http://dx.doi.org/10.1002/ange.201606609]
[130]
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.
[http://dx.doi.org/10.1099/vir.0.81844-0] [PMID: 16894199]
[131]
Zou, J.; Xie, X.; Lee, L.T.; Chandrasekaran, R.; Reynaud, A.; Yap, L.; Wang, Q.Y.; Dong, H.; Kang, C.; Yuan, Z.; Lescar, J.; Shi, P.Y. Dimerization of flavivirus NS4B protein. J. Virol., 2014, 88(6), 3379-3391.
[http://dx.doi.org/10.1128/JVI.02782-13] [PMID: 24390334]
[132]
Zmurko, J.; Neyts, J.; Dallmeier, K. Flaviviral NS4b, chameleon and jack-in-the-box roles in viral replication and pathogenesis, and a molecular target for antiviral intervention. Rev. Med. Virol., 2015, 25(4), 205-223.
[http://dx.doi.org/10.1002/rmv.1835] [PMID: 25828437]
[133]
Zou, G.; Puig-Basagoiti, F.; Zhang, B.; Qing, M.; Chen, L.; Pankiewicz, K.W.; Felczak, K.; Yuan, Z.; Shi, P.Y. A single-amino acid substitution in West Nile virus 2K peptide between NS4A and NS4B confers resistance to lycorine, a flavivirus inhibitor. Virology, 2009, 384(1), 242-252.
[http://dx.doi.org/10.1016/j.virol.2008.11.003]
[134]
Wang, P.; Li, L.F.; Wang, Q.Y.; Shang, L.Q.; Shi, P.Y.; Yin, Z. Anti-dengue-virus activity and structure-activity relationship studies of lycorine derivatives. ChemMedChem, 2014, 9(7), 1522-1533.
[http://dx.doi.org/10.1002/cmdc.201300505] [PMID: 24574246]
[135]
Xie, X.; Wang, Q.Y.; Xu, H.Y.; Qing, M.; Kramer, L.; Yuan, Z.; Shi, P.Y. Inhibition of dengue virus by targeting viral NS4B protein. J. Virol., 2011, 85(21), 11183-11195.
[http://dx.doi.org/10.1128/JVI.05468-11] [PMID: 21865382]
[136]
van Cleef, K.W.R.; Overheul, G.J.; Thomassen, M.C.; Kaptein, S.J.F.; Davidson, A.D.; Jacobs, M.; Neyts, J.; van Kuppeveld, F.J.M.; van Rij, R.P. Identification of a new dengue virus inhibitor that targets the viral NS4B protein and restricts genomic RNA replication. Antiviral Res., 2013, 99(2), 165-171.
[http://dx.doi.org/10.1016/j.antiviral.2013.05.011] [PMID: 23735301]
[137]
Wang, Q.Y.; Dong, H.; Zou, B.; Karuna, R.; Wan, K.F.; Zou, J.; Susila, A.; Yip, A.; Shan, C.; Yeo, K.L.; Xu, H.; Ding, M.; Chan, W.L.; Gu, F.; Seah, P.G.; Liu, W.; Lakshminarayana, S.B.; Kang, C.; Lescar, J.; Blasco, F.; Smith, P.W.; Shi, P.Y. Discovery of dengue virus NS4B inhibitors. J. Virol., 2015, 89(16), 8233-8244.
[http://dx.doi.org/10.1128/JVI.00855-15] [PMID: 26018165]
[138]
van Cleef, K.W.R.; Overheul, G.J.; Thomassen, M.C.; Marjakangas, J.M.; van Rij, R.P. Escape mutations in NS4B render dengue virus insensitive to the antiviral activity of the paracetamol metabolite AM404. Antimicrob. Agents Chemother., 2016, 60(4), 2554-2557.
[http://dx.doi.org/10.1128/AAC.02462-15] [PMID: 26856827]
[139]
Grant, D.; Tan, G.K.; Qing, M.; Ng, J.K.W.; Yip, A.; Zou, G.; Xie, X.; Yuan, Z.; Schreiber, M.J.; Schul, W.; Shi, P.Y.; Alonso, S. A single amino acid in nonstructural protein NS4B confers virulence to dengue virus in AG129 mice through enhancement of viral RNA synthesis. J. Virol., 2011, 85(15), 7775-7787.
[http://dx.doi.org/10.1128/JVI.00665-11] [PMID: 21632767]
[140]
Zou, B.; Chan, W.L.; Ding, M.; Leong, S.Y.; Nilar, S.; Seah, P.G.; Liu, W.; Karuna, R.; Blasco, F.; Yip, A.; Chao, A.; Susila, A.; Dong, H.; Wang, Q.Y.; Xu, H.Y.; Chan, K.; Wan, K.F.; Gu, F.; Diagana, T.T.; Wagner, T.; Dix, I.; Shi, P.Y.; Smith, P.W. Lead optimization of spiropyrazolopyridones: A new and potent class of dengue virus inhibitors. ACS Med. Chem. Lett., 2015, 6(3), 344-348.
[http://dx.doi.org/10.1021/ml500521r] [PMID: 25878766]
[141]
Kounde, C.S.; Yeo, H.Q.; Wang, Q.Y.; Wan, K.F.; Dong, H.; Karuna, R.; Dix, I.; Wagner, T.; Zou, B.; Simon, O.; Bonamy, G.M.C.; Yeung, B.K.S.; Yokokawa, F. Discovery of 2-oxopiperazine dengue inhibitors by scaffold morphing of a phenotypic high-throughput screening hit. Bioorg. Med. Chem. Lett., 2017, 27(6), 1385-1389.
[http://dx.doi.org/10.1016/j.bmcl.2017.02.005] [PMID: 28216045]
[142]
Hernandez-Morales, I.; Geluykens, P.; Clynhens, M.; Strijbos, R.; Goethals, O.; Megens, S.; Verheyen, N.; Last, S.; McGowan, D.; Coesemans, E.; De Boeck, B.; Stoops, B.; Devogelaere, B.; Pauwels, F.; Vandyck, K.; Berke, J.M.; Raboisson, P.; Simmen, K.; Lory, P.; Van Loock, M. Characterization of a dengue NS4B inhibitor originating from an HCV small molecule library. Antiviral Res., 2017, 147, 149-158.
[http://dx.doi.org/10.1016/j.antiviral.2017.10.011] [PMID: 29037976]
[143]
Davidson, A.D. Chapter 2. New insights into flavivirus nonstructural protein 5. Adv. Virus Res., 2009, 74, 41-101.
[http://dx.doi.org/10.1016/S0065-3527(09)74002-3] [PMID: 19698895]
[144]
Malet, H.; Massé, N.; Selisko, B.; Romette, J.L.; Alvarez, K.; Guillemot, J.C.; Tolou, H.; Yap, T.L.; Vasudevan, S.G.; Lescar, J.; Canard, B. The flavivirus polymerase as a target for drug discovery. Antiviral Res., 2008, 80(1), 23-35.
[http://dx.doi.org/10.1016/j.antiviral.2008.06.007] [PMID: 18611413]
[145]
Lim, S.P.; Koh, J.H.K.; Seh, C.C.; Liew, C.W.; Davidson, A.D.; Chua, L.S.; Chandrasekaran, R.; Cornvik, T.C.; Shi, P.Y.; Lescar, J. A crystal structure of the dengue virus non-structural protein 5 (NS5) polymerase delineates interdomain amino acid residues that enhance its thermostability and de novo initiation activities. J. Biol. Chem., 2013, 288(43), 31105-31114.
[http://dx.doi.org/10.1074/jbc.M113.508606] [PMID: 24025331]
[146]
Ray, D.; Shah, A.; Tilgner, M.; Guo, Y.; Zhao, Y.; Dong, H.; Deas, T.S.; Zhou, Y.; Li, H.; Shi, P.Y. West Nile virus 5′-cap structure is formed by sequential guanine N-7 and ribose 2′-O methylations by nonstructural protein 5. J. Virol., 2006, 80(17), 8362-8370.
[http://dx.doi.org/10.1128/JVI.00814-06] [PMID: 16912287]
[147]
Zhou, Y.; Ray, D.; Zhao, Y.; Dong, H.; Ren, S.; Li, Z.; Guo, Y.; Bernard, K.A.; Shi, P.Y.; Li, H. Structure and function of flavivirus NS5 methyltransferase. J. Virol., 2007, 81(8), 3891-3903.
[http://dx.doi.org/10.1128/JVI.02704-06] [PMID: 17267492]
[148]
El Sahili, A.; Lescar, J. Dengue virus non-structural protein 5. Viruses, 2017, 9(4), 91.
[http://dx.doi.org/10.3390/v9040091]
[149]
Dong, H.; Chang, D.C.; Xie, X.; Toh, Y.X.; Chung, K.Y.; Zou, G.; Lescar, J.; Lim, S.P.; Shi, P.Y. Biochemical and genetic characterization of dengue virus methyltransferase. Virology, 2010, 405(2), 568-578.
[http://dx.doi.org/10.1016/j.virol.2010.06.039]
[150]
Züst, R.; Cervantes-Barragan, L.; Habjan, M.; Maier, R.; Neuman, B.W.; Ziebuhr, J.; Szretter, K.J.; Baker, S.C.; Barchet, W.; Diamond, M.S.; Siddell, S.G.; Ludewig, B.; Thiel, V. Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5. Nat. Immunol., 2011, 12(2), 137-143.
[http://dx.doi.org/10.1038/ni.1979] [PMID: 21217758]
[151]
Züst, R.; Dong, H.; Li, X.F.; Chang, D.C.; Zhang, B.; Balakrishnan, T.; Toh, Y.X.; Jiang, T.; Li, S.H.; Deng, Y.Q.; Ellis, B.R.; Ellis, E.M.; Poidinger, M.; Zolezzi, F.; Qin, C.F.; Shi, P.Y.; Fink, K. Rational design of a live attenuated dengue vaccine: 2′-o-methyltransferase mutants are highly attenuated and immunogenic in mice and macaques. PLoS Pathog., 2013, 9(8), e1003521.
[http://dx.doi.org/10.1371/journal.ppat.1003521] [PMID: 23935499]
[152]
Assenberg, R.; Ren, J.; Verma, A.; Walter, T.S.; Alderton, D.; Hurrelbrink, R.J.; Fuller, S.D.; Bressanelli, S.; Owens, R.J.; Stuart, D.I.; Grimes, J.M. Crystal structure of the murray valley encephalitis virus NS5 methyltransferase domain in complex with cap analogues. J. Gen. Virol., 2007, 88(8), 2228-2236.
[http://dx.doi.org/10.1099/vir.0.82757-0] [PMID: 17622627]
[153]
Bollati, M.; Milani, M.; Mastrangelo, E.; Ricagno, S.; Tedeschi, G.; Nonnis, S.; Decroly, E.; Selisko, B.; de Lamballerie, X.; Coutard, B.; Canard, B.; Bolognesi, M. Recognition of RNA cap in the Wesselsbron virus NS5 methyltransferase domain: Implications for RNA-capping mechanisms in Flavivirus. J. Mol. Biol., 2009, 385(1), 140-152.
[http://dx.doi.org/10.1016/j.jmb.2008.10.028] [PMID: 18976670]
[154]
Egloff, M.P.; Benarroch, D.; Selisko, B.; Romette, J-L.; Canard, B. An RNA cap (nucleoside-2′-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization. EMBO J., 2002, 21(11), 2757-2768.
[http://dx.doi.org/10.1093/emboj/21.11.2757] [PMID: 12032088]
[155]
Geiss, B.J.; Thompson, A.A.; Andrews, A.J.; Sons, R.L.; Gari, H.H.; Keenan, S.M.; Peersen, O.B. Analysis of flavivirus NS5 methyltransferase cap binding. J. Mol. Biol., 2009, 385(5), 1643-1654.
[http://dx.doi.org/10.1016/j.jmb.2008.11.058] [PMID: 19101564]
[156]
Jansson, A.M.; Jakobsson, E.; Johansson, P.; Lantez, V.; Coutard, B.; de Lamballerie, X.; Unge, T.; Jones, T.A. Structure of the methyltransferase domain from the modoc virus, a flavivirus with no known vector. Acta Crystallogr. D Biol. Crystallogr., 2009, 65(8), 796-803.
[http://dx.doi.org/10.1107/S0907444909017260] [PMID: 19622863]
[157]
Mastrangelo, E.; Bollati, M.; Milani, M.; Selisko, B.; Peyrane, F.; Canard, B.; Grard, G.; de Lamballerie, X.; Bolognesi, M. Structural bases for substrate recognition and activity in Meaban virus nucleoside-2′-O-methyltransferase. Protein Sci., 2007, 16(6), 1133-1145.
[http://dx.doi.org/10.1110/ps.072758107] [PMID: 17473012]
[158]
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.
[http://dx.doi.org/10.1074/jbc.M110.179184] [PMID: 21147775]
[159]
Yap, L.J.; Luo, D.; Chung, K.Y.; Lim, S.P.; Bodenreider, C.; Noble, C.; Shi, P.Y.; Lescar, J. Crystal structure of the dengue virus methyltransferase bound to a 5′-capped octameric RNA. PLoS One, 2010, 5(9), e12836.
[http://dx.doi.org/10.1371/journal.pone.0012836] [PMID: 20862256]
[160]
Henderson, B.R.; Saeedi, B.J.; Campagnola, G.; Geiss, B.J. Analysis of RNA binding by the dengue virus NS5 RNA capping enzyme. PLoS One, 2011, 6(10), e25795.
[http://dx.doi.org/10.1371/journal.pone.0025795] [PMID: 22022449]
[161]
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.
[http://dx.doi.org/10.1093/nar/gku666] [PMID: 25209234]
[162]
Lim, S.; Wen, D.; Yap, T.; Yan, C.; Lescar, J.; Vasudevan, S. A scintillation proximity assay for dengue virus NS5 2′-O-methyltransferase-kinetic and inhibition analyses. Antiviral Res., 2008, 80(3), 360-369.
[http://dx.doi.org/10.1016/j.antiviral.2008.08.005] [PMID: 18809436]
[163]
Selisko, B.; Peyrane, F.F.; Canard, B.; Alvarez, K.; Decroly, E. Biochemical characterization of the (nucleoside-2'O)-methyltransferase activity of dengue virus protein NS5 using purified capped RNA oligonucleotides 7MeGpppACn and GpppACn. J. Gen. Virol., 2010, 91(1), 112-121.
[http://dx.doi.org/10.1099/vir.0.015511-0] [PMID: 19776234]
[164]
Chung, K.Y.; Dong, H.; Chao, A.T.; Shi, P.Y.; Lescar, J.; Lim, S.P. Higher catalytic efficiency of N-7-methylation is responsible for processive N-7 and 2′-O methyltransferase activity in dengue virus. Virology, 2010, 402(1), 52-60.
[http://dx.doi.org/10.1016/j.virol.2010.03.011] [PMID: 19776122]
[165]
Barral, K.; Sallamand, C.; Petzold, C.; Coutard, B.; Collet, A.; Thillier, Y.; Zimmermann, J.; Vasseur, J.J.; Canard, B.; Rohayem, J.; Debart, F.; Decroly, E. Development of specific dengue virus 2′-O- and N7-methyltransferase assays for antiviral drug screening. Antiviral Res., 2013, 99(3), 292-300.
[http://dx.doi.org/10.1016/j.antiviral.2013.06.001] [PMID: 23769894]
[166]
Dong, H.; Liu, L.; Zou, G.; Zhao, Y.; Li, Z.; Lim, S.P.; Shi, P.Y.; Li, H. Structural and functional analyses of a conserved hydrophobic pocket of flavivirus methyltransferase. J. Biol. Chem., 2010, 285(42), 32586-32595.
[http://dx.doi.org/10.1074/jbc.M110.129197] [PMID: 20685660]
[167]
Noble, C.G.; Li, S.H.; Dong, H.; Chew, S.H.; Shi, P.Y. Crystal structure of dengue virus methyltransferase without S-adenosyl-L-methionine. Antiviral Res., 2014, 111, 78-81.
[http://dx.doi.org/10.1016/j.antiviral.2014.09.003] [PMID: 25241250]
[168]
Brecher, M.B.; Li, Z.; Zhang, J.; Chen, H.; Lin, Q.; Liu, B.; Li, H. Refolding of a fully functional flavivirus methyltransferase revealed that S-adenosyl methionine but not S-adenosyl homocysteine is copurified with flavivirus methyltransferase. Protein Sci., 2015, 24(1), 117-128.
[http://dx.doi.org/10.1002/pro.2594] [PMID: 25352331]
[169]
Cannalire, R.; Tarantino, D.; Astolfi, A.; Barreca, M.L.; Sabatini, S.; Massari, S.; Tabarrini, O.; Milani, M.; Querat, G.; Mastrangelo, E.; Manfroni, G.; Cecchetti, V. Functionalized 2,1-benzothiazine 2,2-dioxides as new inhibitors of Dengue NS5 RNA-dependent RNA polymerase. Eur. J. Med. Chem., 2018, 143, 1667-1676.
[http://dx.doi.org/10.1016/j.ejmech.2017.10.064] [PMID: 29137867]
[170]
Kaptein, S.J.F.; Vincetti, P.; Crespan, E.; Rivera, J.I.A.; Costantino, G.; Maga, G.; Neyts, J.; Radi, M. Identification of broad-spectrum dengue/zika virus replication inhibitors by functionalization of quinoline and 2,6-diaminopurine scaffolds. ChemMedChem, 2018, 13(14), 1371-1376.
[http://dx.doi.org/10.1002/cmdc.201800178] [PMID: 29740962]
[171]
Benmansour, F.; Eydoux, C.; Querat, G.; de Lamballerie, X.; Canard, B.; Alvarez, K.; Guillemot, J.C.; Barral, K. Novel 2-phenyl-5-[(E)-2-(thiophen-2-yl)ethenyl]-1,3,4-oxadiazole and 3-phenyl-5-[(E)-2-(thiophen-2-yl)ethenyl]-1,2,4-oxadiazole derivatives as dengue virus inhibitors targeting NS5 polymerase. Eur. J. Med. Chem., 2016, 109, 146-156.
[http://dx.doi.org/10.1016/j.ejmech.2015.12.046] [PMID: 26774922]
[172]
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 Chemother., 2016, 60(1), 600-608.
[http://dx.doi.org/10.1128/AAC.02203-15] [PMID: 26574011]
[173]
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.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00143] [PMID: 26984786]
[174]
Lim, S.P.; Noble, C.G.; Seh, C.C.; Soh, T.S.; El Sahili, A.; Chan, G.K.Y.; 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.
[http://dx.doi.org/10.1371/journal.ppat.1005737] [PMID: 27500641]
[175]
Madhvi, A.; Hingane, S.; Srivastav, R.; Joshi, N.; Subramani, C.; Muthumohan, R.; Khasa, R.; Varshney, S.; Kalia, M.; Vrati, S.; Surjit, M.; Ranjith-Kumar, C.T. A screen for novel hepatitis C virus RdRp inhibitor identifies a broad-spectrum antiviral compound. Sci. Rep., 2017, 7(1), 5816.
[http://dx.doi.org/10.1038/s41598-017-04449-3] [PMID: 28127051]
[176]
Wang, G.; Lim, S.P.; Chen, Y.L.; Hunziker, J.; Rao, R.; Gu, F.; Seh, C.C.; Ghafar, N.A.; Xu, H.; Chan, K.; Lin, X.; Saunders, O.L.; Fenaux, M.; Zhong, W.; Shi, P.Y.; Yokokawa, F. Structure-activity relationship of uridine-based nucleoside phosphoramidate prodrugs for inhibition of dengue virus RNA-dependent RNA polymerase. Bioorg. Med. Chem. Lett., 2018, 28(13), 2324-2327.
[http://dx.doi.org/10.1016/j.bmcl.2018.04.069] [PMID: 29801997]
[177]
Coulerie, P.; Maciuk, A.; Eydoux, C.; Hnawia, E.; Lebouvier, N.; Figadère, B.; Guillemot, J-C.; Nour, M. New inhibitors of the DENV-NS 5 RdRp from carpolepis laurifolia as potential antiviral drugs for dengue treatment. Rec. Nat. Prod., 2014, 8(3), 286.
[178]
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.
[http://dx.doi.org/10.1016/j.antiviral.2016.09.007] [PMID: 27649989]
[179]
Yao, X.; Ling, Y.; Guo, S.; He, S.; Wang, J.; Zhang, Q.; Wu, W.; Zou, M.; Zhang, T.; Nandakumar, K.S.; Chen, X.; Liu, S. Inhibition of dengue viral infection by diasarone-I is associated with 2'O methyltransferase of NS5. Eur. J. Pharmacol., 2018, 821, 11-20.
[http://dx.doi.org/10.1016/j.ejphar.2017.12.029]
[180]
Vernekar, S.K.V.; Qiu, L.; Zhang, J.; Kankanala, J.; Li, H.; Geraghty, R.J.; Wang, Z. 5′-Silylated 3′-1,2,3-triazolyl thymidine analogues as inhibitors of west nile virus and dengue virus. J. Med. Chem., 2015, 58(9), 4016-4028.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00327] [PMID: 25909386]
[181]
Benmansour, F.; Trist, I.; Coutard, B.; Decroly, E.; Querat, G.; Brancale, A.; Barral, K. Discovery of novel dengue virus NS5 methyltransferase non-nucleoside inhibitors by fragment-based drug design. Eur. J. Med. Chem., 2017, 125, 865-880.
[http://dx.doi.org/10.1016/j.ejmech.2016.10.007] [PMID: 27750202]
[182]
Brecher, M.; Chen, H.; Liu, B.; Banavali, N.K.; Jones, S.A.; Zhang, J.; Li, Z.; Kramer, L.D.; Li, H. Novel broad spectrum inhibitors targeting the flavivirus methyltransferase. PLoS One, 2015, 10(6), e0130062.
[http://dx.doi.org/10.1371/journal.pone.0130062] [PMID: 26098995]
[183]
Beesetti, H.; Khanna, N.; Swaminathan, S. Investigational drugs in early development for treating dengue infection. Expert Opin. Investig. Drugs, 2016, 25(9), 1059-1069.
[http://dx.doi.org/10.1080/13543784.2016.1201063] [PMID: 27322111]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy