{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:31:39Z","timestamp":1790267499114,"version":"4.1.0"},"reference-count":113,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T00:00:00Z","timestamp":1414800000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2014,11]]},"DOI":"10.1016\/j.ejmech.2014.10.010","type":"journal-article","created":{"date-parts":[[2014,10,7]],"date-time":"2014-10-07T21:57:00Z","timestamp":1412719020000},"page":"677-702","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":42,"special_numbering":"C","title":["A perspective on targeting non-structural proteins to combat neglected tropical diseases: Dengue, West Nile and Chikungunya viruses"],"prefix":"10.1016","volume":"87","author":[{"given":"Soumendranath","family":"Bhakat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson","family":"Karubiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkatesan","family":"Jayaprakash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud E.S.","family":"Soliman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2014.10.010_bib1","article-title":"Neglected tropical diseases: becoming less neglected","volume":"383","year":"2014","journal-title":"Lancet"},{"key":"10.1016\/j.ejmech.2014.10.010_bib2","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1371\/journal.pmed.0030102","article-title":"Incorporating a rapid-impact package for neglected tropical diseases with programs for HIV\/AIDS, tuberculosis, and malaria \u2013 a comprehensive pro-poor health policy and strategy for the developing world","volume":"3","author":"Hotez","year":"2006","journal-title":"Plos Med."},{"key":"10.1016\/j.ejmech.2014.10.010_bib3","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0000247","article-title":"Why arboviruses can Be neglected tropical diseases","volume":"2","author":"LaBeaud","year":"2008","journal-title":"Plos Neglected Trop. Dis."},{"key":"10.1016\/j.ejmech.2014.10.010_bib4","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/S0188-4409(02)00378-8","article-title":"The global emergence\/resurgence of arboviral diseases as public health problems","volume":"33","author":"Gubler","year":"2002","journal-title":"Arch. Med. Res."},{"key":"10.1016\/j.ejmech.2014.10.010_bib5","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1039\/c4md00011k","article-title":"The role of modern drug discovery in the fight against neglected and tropical diseases","volume":"5","author":"Burrows","year":"2014","journal-title":"MedChemComm"},{"key":"10.1016\/j.ejmech.2014.10.010_bib6","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/j.micinf.2009.05.005","article-title":"Aedes albopictus, an arbovirus vector: from the darkness to the light","volume":"11","author":"Paupy","year":"2009","journal-title":"Microbes Infect."},{"key":"10.1016\/j.ejmech.2014.10.010_bib7","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.4155\/fmc.10.211","article-title":"Structure-based antivirals for emerging and neglected RNA viruses: an emerging field for medicinal chemistry in academia","volume":"2","author":"Hilgenfeld","year":"2010","journal-title":"Future Med. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib8","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1097\/QAI.0b013e3182657990","article-title":"N348I in HIV-1 reverse transcriptase counteracts the synergy between zidovudine and nevirapine","volume":"61","author":"Yap","year":"2012","journal-title":"Jaids J. Acquir. Immune Defic. Syndrom."},{"key":"10.1016\/j.ejmech.2014.10.010_bib9","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/nm0703-867","article-title":"Twenty years of therapy for HIV-1 infection","volume":"9","author":"Pomerantz","year":"2003","journal-title":"Nat. Med."},{"key":"10.1016\/j.ejmech.2014.10.010_bib10","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/312763a0","article-title":"The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus","volume":"312","author":"Dalgleish","year":"1984","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2014.10.010_bib11","doi-asserted-by":"crossref","first-page":"7911","DOI":"10.1021\/jm900652e","article-title":"The medicinal chemistry of dengue fever","volume":"52","author":"Stevens","year":"2009","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib12","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nrmicro2950","article-title":"West Nile virus infection and immunity","volume":"11","author":"Suthar","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"10.1016\/j.ejmech.2014.10.010_bib13","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.patbio.2008.02.016","article-title":"The biology of chikungunya: a brief review of what we still do not know","volume":"57","author":"Pardigon","year":"2009","journal-title":"Pathol. Biol."},{"key":"10.1016\/j.ejmech.2014.10.010_bib14","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1099\/vir.0.82858-0","article-title":"Changing patterns of chikungunya virus: re-emergence of a zoonotic arbovirus","volume":"88","author":"Powers","year":"2007","journal-title":"J.\u00a0Gen. Virol."},{"key":"10.1016\/j.ejmech.2014.10.010_bib15","article-title":"Drug discovery for neglected diseases","volume":"7","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ejmech.2014.10.010_bib16","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0001827","article-title":"Open source drug discovery in practice: a case study","volume":"6","author":"Ardal","year":"2012","journal-title":"Plos Neglected Trop. Dis."},{"key":"10.1016\/j.ejmech.2014.10.010_bib17","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1517\/17460440902762802","article-title":"Targeting the non-structural proteins of hepatitis C virus: beyond hepatitis C virus protease and polymerase","volume":"4","author":"Holler","year":"2009","journal-title":"Expert Opin. Drug Discov."},{"key":"10.1016\/j.ejmech.2014.10.010_bib18","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1111\/j.1476-5381.2010.01127.x","article-title":"Principles of early drug discovery","volume":"162","author":"Hughes","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejmech.2014.10.010_bib19","doi-asserted-by":"crossref","first-page":"7367","DOI":"10.1128\/JVI.00632-13","article-title":"The small molecules AZD0530 and dasatinib inhibit dengue virus RNA replication via Fyn kinase","volume":"87","author":"de Wispelaere","year":"2013","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.ejmech.2014.10.010_bib20","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/nrd3368","article-title":"Impact of high-throughput screening in biomedical research","volume":"10","author":"Macarron","year":"2011","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ejmech.2014.10.010_bib21","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1038\/nm.2471","article-title":"The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine","volume":"17","author":"Tu","year":"2011","journal-title":"Nat. Med."},{"key":"10.1016\/j.ejmech.2014.10.010_bib22","doi-asserted-by":"crossref","first-page":"3488","DOI":"10.2174\/13816128113199990636","article-title":"Recent advances in the development of antiviral agents using computer-aided structure based approaches","volume":"20","author":"Kumar","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"10.1016\/j.ejmech.2014.10.010_bib23","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.3390\/v5122977","article-title":"West Nile virus drug discovery","volume":"5","author":"Lim","year":"2013","journal-title":"Viruses"},{"key":"10.1016\/j.ejmech.2014.10.010_bib24","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1021\/jm400460d","article-title":"Chikungunya virus: emerging targets and new opportunities for medicinal chemistry","volume":"57","author":"Rashad","year":"2014","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib25","doi-asserted-by":"crossref","first-page":"327","DOI":"10.2174\/1871526510909030327","article-title":"New approaches to structure-based discovery of dengue protease inhibitors","volume":"9","author":"Tomlinson","year":"2009","journal-title":"Infect. Disord. Drug Targets"},{"key":"10.1016\/j.ejmech.2014.10.010_bib26","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/nsmb1073","article-title":"Structural basis for the activation of flaviviral NS3 proteases from dengue and West Nile virus","volume":"13","author":"Erbel","year":"2006","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.ejmech.2014.10.010_bib27","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1128\/JVI.06225-11","article-title":"Ligand-bound structures of the dengue virus protease Reveal the active conformation","volume":"86","author":"Noble","year":"2012","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.ejmech.2014.10.010_bib28","doi-asserted-by":"crossref","first-page":"4140","DOI":"10.1016\/j.bmc.2012.04.055","article-title":"Inhibitors of Dengue virus and West Nile virus proteases based on the aminobenzamide scaffold","volume":"20","author":"Aravapalli","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib29","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1128\/JVI.01788-07","article-title":"Crystal structure of the NS3 protease-helicase from dengue virus","volume":"82","author":"Luo","year":"2008","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.ejmech.2014.10.010_bib30","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.jmb.2007.07.005","article-title":"Structural and functional analysis of methylation and 5\u2032-RNA sequence requirements of short capped RNAs by the methyltransferase domain of dengue virus NS5","volume":"372","author":"Egloff","year":"2007","journal-title":"J.\u00a0Mol. Biol."},{"key":"10.1016\/j.ejmech.2014.10.010_bib31","doi-asserted-by":"crossref","first-page":"4753","DOI":"10.1128\/JVI.02283-06","article-title":"Crystal structure of the dengue virus RNA-dependent RNA polymerase catalytic domain at 1.85-Angstrom resolution","volume":"81","author":"Yap","year":"2007","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.ejmech.2014.10.010_bib32","doi-asserted-by":"crossref","first-page":"4285","DOI":"10.1073\/pnas.1322036111","article-title":"Structural basis of flavivirus NS1 assembly and antibody recognition","volume":"111","author":"Edeling","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"10.1016\/j.ejmech.2014.10.010_bib33","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/cmdc.201200497","article-title":"Development and characterization of new peptidomimetic inhibitors of the west nile virus NS2B-NS3 protease","volume":"8","author":"Hammamy","year":"2013","journal-title":"ChemMedChem"},{"key":"10.1016\/j.ejmech.2014.10.010_bib34","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1021\/ci100275a","article-title":"Assessing the performance of the MM\/PBSA and MM\/GBSA methods. 1. The accuracy of binding free Energy calculations based on molecular dynamics simulations","volume":"51","author":"Hou","year":"2011","journal-title":"J.\u00a0Chem. Info. Model."},{"key":"10.1016\/j.ejmech.2014.10.010_bib35","doi-asserted-by":"crossref","first-page":"10678","DOI":"10.1074\/jbc.M607273200","article-title":"Crystal structure of the RNA polymerase domain of the West Nile virus non-structural protein 5","volume":"282","author":"Malet","year":"2007","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib36","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.antiviral.2008.06.007","article-title":"The flavivirus polymerase as a target for drug discovery","volume":"80","author":"Malet","year":"2008","journal-title":"Antivir. Res."},{"key":"10.1016\/j.ejmech.2014.10.010_bib37","doi-asserted-by":"crossref","first-page":"3712","DOI":"10.1021\/jp994072s","article-title":"Modification of the generalized Born model suitable for macromolecules","volume":"104","author":"Onufriev","year":"2000","journal-title":"J.\u00a0Phys. Chem. B"},{"key":"10.1016\/j.ejmech.2014.10.010_bib38","doi-asserted-by":"crossref","first-page":"6534","DOI":"10.1128\/JVI.00189-09","article-title":"The Crystal structures of chikungunya and Venezuelan Equine encephalitis virus nsP3 macro domains define a conserved adenosine binding pocket","volume":"83","author":"Malet","year":"2009","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.ejmech.2014.10.010_bib39","doi-asserted-by":"crossref","first-page":"e1002383","DOI":"10.1371\/journal.ppat.1002383","article-title":"SH3 domain-mediated recruitment of host cell amphiphysins by alphavirus nsP3 promotes viral RNA replication","volume":"7","author":"Neuvonen","year":"2011","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.ejmech.2014.10.010_bib40","doi-asserted-by":"crossref","first-page":"2986","DOI":"10.1111\/j.1742-4658.2007.05831.x","article-title":"Progress for dengue virus diseases - towards the NS2B-NS3pro inhibition for a therapeutic-based approach","volume":"274","author":"Melino","year":"2007","journal-title":"Febs J."},{"key":"10.1016\/j.ejmech.2014.10.010_bib41","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1128\/AAC.00855-10","article-title":"Novel dengue virus-specific NS2B\/NS3 protease inhibitor, BP2109, discovered by a high-throughput screening assay","volume":"55","author":"Yang","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2014.10.010_bib42","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1128\/AAC.01281-13","article-title":"A\u00a0novel dengue virus inhibitor, BP13944, discovered by high-throughput screening with dengue virus peplicon cells selects for resistance in the viral NS2B\/NS3 protease","volume":"58","author":"Yang","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2014.10.010_bib43","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s10822-011-9418-0","article-title":"Structure-guided fragment-based in silico drug design of dengue protease inhibitors","volume":"25","author":"Knehans","year":"2011","journal-title":"J.\u00a0Comput. Aided Mol. Des."},{"key":"10.1016\/j.ejmech.2014.10.010_bib44","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.antiviral.2010.12.006","article-title":"Anthracene-based inhibitors of dengue virus NS2B-NS3 protease","volume":"89","author":"Tomlinson","year":"2011","journal-title":"Antivir. Res."},{"key":"10.1016\/j.ejmech.2014.10.010_bib45","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.bbrc.2013.09.078","article-title":"A\u00a0small compound targeting the interaction between nonstructural proteins 2B and 3 inhibits dengue virus replication","volume":"440","author":"Pambudi","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ejmech.2014.10.010_bib46","doi-asserted-by":"crossref","first-page":"6278","DOI":"10.1021\/jm300146f","article-title":"Discovery of novel small molecule inhibitors of dengue viral NS2B-NS3 protease using virtual screening and scaffold hopping","volume":"55","author":"Deng","year":"2012","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib47","doi-asserted-by":"crossref","first-page":"15600","DOI":"10.3390\/molecules181215600","article-title":"In\u00a0vitro evaluation of novel inhibitors against the NS2B-NS3 protease of dengue fever virus type 4","volume":"18","author":"Thi Thanh Hanh","year":"2013","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2014.10.010_bib48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/cbdd.12122","article-title":"Rational discovery of dengue type 2 non-competitive inhibitors","volume":"82","author":"Heh","year":"2013","journal-title":"Chem. Biol. Drug Des."},{"key":"10.1016\/j.ejmech.2014.10.010_bib49","doi-asserted-by":"crossref","first-page":"3337","DOI":"10.1016\/j.bmcl.2005.12.075","article-title":"Inhibitory activity of cyclohexenyl chalcone derivatives and flavonoids of fingerroot, Boesenbergia rotunda (L.), towards dengue-2 virus NS3 protease","volume":"16","author":"Kiat","year":"2006","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2014.10.010_bib50","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.antiviral.2012.10.009","article-title":"Characterization of 8-hydroxyquinoline derivatives containing aminobenzothiazole as inhibitors of dengue virus type 2 protease in\u00a0vitro","volume":"97","author":"Lai","year":"2013","journal-title":"Antivir. Res."},{"key":"10.1016\/j.ejmech.2014.10.010_bib51","doi-asserted-by":"crossref","first-page":"4067","DOI":"10.1016\/j.bmc.2011.05.015","article-title":"Synthesis and biological evaluation of alpha-ketoamides as inhibitors of the Dengue virus protease with antiviral activity in cell-culture","volume":"19","author":"Steuer","year":"2011","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib52","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/j.bmc.2011.12.047","article-title":"Inhibition of Dengue virus and West Nile virus proteases by click chemistry-derived benz d isothiazol-3(2H)-one derivatives","volume":"20","author":"Tiew","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib53","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2334-12-314","article-title":"Inhibition of dengue NS2B-NS3 protease and viral replication in Vero cells by recombinant retrocyclin-1","volume":"12","author":"Rothan","year":"2012","journal-title":"BMC Infect. Dis."},{"key":"10.1016\/j.ejmech.2014.10.010_bib54","doi-asserted-by":"crossref","first-page":"8389","DOI":"10.1021\/jm400828u","article-title":"Thiazolidinone-peptide hybrids as dengue virus protease inhibitors with antiviral activity in cell culture","volume":"56","author":"Nitsche","year":"2013","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib55","doi-asserted-by":"crossref","first-page":"7318","DOI":"10.1016\/j.bmc.2011.10.061","article-title":"Arylcyanoacrylamides as inhibitors of the Dengue and West Nile virus proteases","volume":"19","author":"Nitsche","year":"2011","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib56","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.bmcl.2005.09.049","article-title":"Peptide inhibitors of dengue virus NS3 protease. Part 2: SAR study of tetrapeptide aldehyde inhibitors","volume":"16","author":"Yin","year":"2006","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2014.10.010_bib57","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1093\/cid\/cis501","article-title":"Frequent emergence of N348I in HIV-1 subtype C reverse transcriptase with failure of initial therapy reduces susceptibility to reverse-transcriptase inhibitors","volume":"55","author":"Brehm","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"10.1016\/j.ejmech.2014.10.010_bib58","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1002\/1096-987X(200012)21:16<1433::AID-JCC2>3.0.CO;2-P","article-title":"Aspects of hybrid QM\/MM calculations: the treatment of the QM\/MM interface region and geometry optimization with an application to chorismate mutase","volume":"21","author":"Hall","year":"2000","journal-title":"J.\u00a0Comput. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib59","doi-asserted-by":"crossref","first-page":"6549","DOI":"10.1016\/j.bmcl.2013.10.071","article-title":"Discovery and SAR studies of methionine-proline anilides as dengue virus NS2B-NS3 protease inhibitors","volume":"23","author":"Zhou","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2014.10.010_bib60","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.bbrc.2013.03.139","article-title":"Design and evaluation of substrate-based octapeptide and non substrate-based tetrapeptide inhibitors of dengue virus NS2B-NS3 proteases","volume":"434","author":"Prusis","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ejmech.2014.10.010_bib61","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3851\/IMP1767","article-title":"Small molecule pan-dengue and West Nile virus NS3 protease inhibitors","volume":"21","author":"Cregar-Hernandez","year":"2011","journal-title":"Antivir. Chem. Chemother."},{"key":"10.1016\/j.ejmech.2014.10.010_bib62","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1016\/j.bmc.2009.12.026","article-title":"Synthesis and disulfide bond connectivity-activity studies of a kalata B1-inspired cyclopeptide against dengue NS2B-NS3 protease","volume":"18","author":"Gao","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib63","doi-asserted-by":"crossref","first-page":"35638","DOI":"10.1074\/jbc.M400460200","article-title":"A\u00a0structural basis for the inhibition of the NS5 dengue virus mRNA 2\u2032-O-Methyltransferase domain by ribavirin 5\u2032-triphosphate","volume":"279","author":"Benarroch","year":"2004","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib64","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1128\/AAC.36.2.435","article-title":"Antiviral activities of ribavirin, 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide, and 6'-(R)-6\u2032-C-methylneplanocin A against several ortho- and paramyxoviruses","volume":"36","author":"Shigeta","year":"1992","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2014.10.010_bib65","doi-asserted-by":"crossref","first-page":"20435","DOI":"10.1073\/pnas.0907010106","article-title":"An adenosine nucleoside inhibitor of dengue virus","volume":"106","author":"Yin","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ejmech.2014.10.010_bib66","doi-asserted-by":"crossref","first-page":"5967","DOI":"10.1021\/jm9006142","article-title":"Discovery of novel types of inhibitors of s-adenosylmethionine synthesis by virtual screening","volume":"52","author":"Taylor","year":"2009","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib67","doi-asserted-by":"crossref","first-page":"7795","DOI":"10.1016\/j.bmc.2007.08.049","article-title":"Virtual screening and bioassay study of novel inhibitors for dengue virus mRNA cap (nucleoside-2\u2032 O)-methyltransferase","volume":"15","author":"Luzhkov","year":"2007","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib68","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1021\/np200715v","article-title":"Alkylated flavanones from the bark of Cryptocarya chartacea as dengue virus NS5 polymerase inhibitors","volume":"74","author":"Allard","year":"2011","journal-title":"J.\u00a0Nat. Prod."},{"key":"10.1016\/j.ejmech.2014.10.010_bib69","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1055\/s-0031-1298355","article-title":"Biflavonoids of dacrydium balansae with potent inhibitory activity on dengue 2 NS5 polymerase","volume":"78","author":"Coulerie","year":"2012","journal-title":"Planta Medica"},{"key":"10.1016\/j.ejmech.2014.10.010_bib70","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1128\/AAC.02251-12","article-title":"Novel benzoxazole inhibitor of dengue virus replication that targets the NS3 helicase","volume":"57","author":"Byrd","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2014.10.010_bib71","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.antiviral.2013.05.011","article-title":"Identification of a new dengue virus inhibitor that targets the viral NS4B protein and restricts genomic RNA replication","volume":"99","author":"van Cleef","year":"2013","journal-title":"Antivir. Res."},{"key":"10.1016\/j.ejmech.2014.10.010_bib72","doi-asserted-by":"crossref","first-page":"6585","DOI":"10.1021\/jm0607606","article-title":"Peptide inhibitors of West Nile NS3 protease: SAR study of tetrapeptide aldehyde inhibitors","volume":"49","author":"Knox","year":"2006","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib73","doi-asserted-by":"crossref","first-page":"5714","DOI":"10.1021\/jm800503y","article-title":"Potent cationic inhibitors of West Nile Virus NS2B\/NS3 protease with serum stability, cell permeability and antiviral activity","volume":"51","author":"Stoermer","year":"2008","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib74","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.antiviral.2011.07.002","article-title":"Tripeptide inhibitors of dengue and West Nile virus NS2B-NS3 protease","volume":"92","author":"Schueller","year":"2011","journal-title":"Antivir. Res."},{"key":"10.1016\/j.ejmech.2014.10.010_bib75","doi-asserted-by":"crossref","first-page":"3130","DOI":"10.1016\/j.ejmech.2011.04.055","article-title":"Novel agmatine and agmatine-like peptidomimetic inhibitors of the West Nile virus NS2B\/NS3 serine protease","volume":"46","author":"Lim","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib76","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.ejmech.2012.12.043","article-title":"Novel agmatine dipeptide inhibitors against the West Nile virus NS2B\/NS3 protease: a P3 and N-cap optimization study","volume":"62","author":"Lim","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib77","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.01525-08","article-title":"Identification and biochemical characterization of small-molecule inhibitors of west nile virus serine protease by a high-throughput screen","volume":"53","author":"Mueller","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2014.10.010_bib78","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1021\/cc100091h","article-title":"Design, synthesis, and in\u00a0vitro evaluation of potential west nile virus protease inhibitors based on the 1-Oxo-1,2,3,4-tetrahydroisoquinoline and 1-Oxo-1,2-dihydroisoquinoline scaffolds","volume":"12","author":"Dou","year":"2010","journal-title":"J.\u00a0Comb. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib79","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1007\/s00705-010-0702-4","article-title":"Identification of palmatine as an inhibitor of West Nile virus","volume":"155","author":"Jia","year":"2010","journal-title":"Arch. Virol."},{"key":"10.1016\/j.ejmech.2014.10.010_bib80","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1089\/adt.2007.101","article-title":"HTS identifies novel and specific uncompetitive inhibitors of the two-component NS2B-NS3 proteinase of West Nile virus","volume":"5","author":"Johnston","year":"2007","journal-title":"Assay Drug Dev. Technol."},{"key":"10.1016\/j.ejmech.2014.10.010_bib81","doi-asserted-by":"crossref","first-page":"5773","DOI":"10.1016\/j.bmcl.2009.07.150","article-title":"Structure-activity relationship and improved hydrolytic stability of pyrazole derivatives that are allosteric inhibitors of West Nile Virus NS2B-NS3 proteinase","volume":"19","author":"Sidique","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2014.10.010_bib82","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1002\/cmdc.201300114","article-title":"Synthesis and invitro evaluation of West Nile virus protease inhibitors based on the 2-{6-2-(5-Phenyl-4H-{1,2,4 triazol-3-ylsulfanyl)acetylamino benzothiazo l-2-ylsulfanyl}acetamide Scaffold","volume":"8","author":"Samanta","year":"2013","journal-title":"ChemMedChem"},{"key":"10.1016\/j.ejmech.2014.10.010_bib83","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1002\/cmdc.201300244","article-title":"Synthesis and in\u00a0vitro evaluation of west nile virus protease inhibitors based on the 1,3,4,5-tetrasubstituted 1H-Pyrrol-2(5H)-one scaffold","volume":"8","author":"Gao","year":"2013","journal-title":"ChemMedChem"},{"key":"10.1016\/j.ejmech.2014.10.010_bib84","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.antiviral.2011.12.003","article-title":"Use of parallel validation high-throughput screens to reduce false positives and identify novel dengue NS2B-NS3 protease inhibitors","volume":"93","author":"Tomlinson","year":"2012","journal-title":"Antivir. Res."},{"key":"10.1016\/j.ejmech.2014.10.010_bib85","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1089\/adt.2010.0309","article-title":"Virtual ligand screening of the national Cancer Institute (NCI) compound library leads to the allosteric inhibitory scaffolds of the west nile virus NS3 proteinase","volume":"9","author":"Shiryaev","year":"2011","journal-title":"Assay Drug Dev. Technol."},{"key":"10.1016\/j.ejmech.2014.10.010_bib86","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.antiviral.2012.12.012","article-title":"Selective inhibition of the West Nile virus methyltransferase by nucleoside analogs","volume":"97","author":"Chen","year":"2013","journal-title":"Antivir. Res."},{"key":"10.1016\/j.ejmech.2014.10.010_bib87","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1093\/jac\/dks147","article-title":"Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug","volume":"67","author":"Mastrangelo","year":"2012","journal-title":"J.\u00a0Antimicrob. Chemother."},{"key":"10.1016\/j.ejmech.2014.10.010_bib88","doi-asserted-by":"crossref","first-page":"4149","DOI":"10.1021\/jm030842j","article-title":"Ring-expanded (\u201cfat\u201d) nucleoside and nucleotide analogues exhibit potent in\u00a0vitro activity against Flaviviridae NTPases\/helicases, including those of the West Nile virus, hepatitis C virus, and Japanese encephalitis virus","volume":"46","author":"Zhang","year":"2003","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib89","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1128\/AAC.46.5.1231-1239.2002","article-title":"Characterization of imidazo[4,5-d]pyridazine nucleosides as modulators of unwinding reaction mediated by West Nile virus nucleoside triphosphatase\/helicase: evidence for activity on the level of substrate and\/or enzyme","volume":"46","author":"Borowski","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2014.10.010_bib90","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.antiviral.2013.01.002","article-title":"Computer-aided identification, design and synthesis of a novel series of compounds with selective antiviral activity against chikungunya virus","volume":"98","author":"Bassetto","year":"2013","journal-title":"Antivir. Res."},{"key":"10.1016\/j.ejmech.2014.10.010_bib91","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s00894-011-1018-3","article-title":"Homology modeling, molecular dynamics, e-pharmacophore mapping and docking study of Chikungunya virus nsP2 protease","volume":"18","author":"Singh","year":"2012","journal-title":"J.\u00a0Mol. Model."},{"key":"10.1016\/j.ejmech.2014.10.010_bib92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00894-014-2216-6","article-title":"Discovery of in silico hits targeting the nsP3 macro domain of chikungunya virus","volume":"20","author":"Nguyen","year":"2014","journal-title":"J.\u00a0Mol. Model."},{"key":"10.1016\/j.ejmech.2014.10.010_bib93","doi-asserted-by":"crossref","first-page":"6720","DOI":"10.1021\/ja00130a011","article-title":"Multiple molecular dynamics simulations of the anticodon loop of tRNAAsp in aqueous solution with counterions","volume":"117","author":"Auffinger","year":"1995","journal-title":"J.\u00a0Am. Chem. Soc."},{"key":"10.1016\/j.ejmech.2014.10.010_bib94","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/jcc.540040211","article-title":"CHARMM - a program for macromolecular energy, minimization, and dynamics calculations","volume":"4","author":"Brooks","year":"1983","journal-title":"J.\u00a0Comput. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib95","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.antiviral.2010.02.326","article-title":"The VIZIER project: overview; expectations; and achievements","volume":"87","author":"Coutard","year":"2010","journal-title":"Antivir. Res."},{"key":"10.1016\/j.ejmech.2014.10.010_bib96","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.antiviral.2009.11.009","article-title":"Structure and functionality in flavivirus NS-proteins: perspectives for drug design","volume":"87","author":"Bollati","year":"2010","journal-title":"Antivir. Res."},{"key":"10.1016\/j.ejmech.2014.10.010_bib97","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1006\/jmbi.1999.2843","article-title":"Analysis methods for comparison of multiple molecular dynamics trajectories: applications to protein unfolding pathways and denatured ensembles","volume":"290","author":"Kazmirski","year":"1999","journal-title":"J.\u00a0Mol. Biol."},{"key":"10.1016\/j.ejmech.2014.10.010_bib98","doi-asserted-by":"crossref","first-page":"3072","DOI":"10.1529\/biophysj.104.050286","article-title":"Comparison of multiple molecular dynamics trajectories calculated for the drug-resistant HIV-1 integrase T66I\/M154I catalytic domain","volume":"88","author":"Brigo","year":"2005","journal-title":"Biophys. J."},{"key":"10.1016\/j.ejmech.2014.10.010_bib99","doi-asserted-by":"crossref","first-page":"2744","DOI":"10.1021\/cb400612h","article-title":"Allosteric inhibition of the NS2B-NS3 protease from dengue virus","volume":"8","author":"Yildiz","year":"2013","journal-title":"Acs Chem. Biol."},{"key":"10.1016\/j.ejmech.2014.10.010_bib100","doi-asserted-by":"crossref","first-page":"5291","DOI":"10.1128\/JVI.00045-13","article-title":"Conformational flexibility of the dengue virus RNA-dependent RNA polymerase revealed by a complex with an inhibitor","volume":"87","author":"Noble","year":"2013","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.ejmech.2014.10.010_bib101","doi-asserted-by":"crossref","first-page":"6233","DOI":"10.1074\/jbc.M110.179184","article-title":"Small molecule inhibitors that selectively block dengue virus methyltransferase","volume":"286","author":"Lim","year":"2011","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib102","doi-asserted-by":"crossref","first-page":"18817","DOI":"10.1074\/jbc.M109.090936","article-title":"Flexibility between the protease and helicase domains of the dengue virus NS3 protein conferred by the linker region and its functional implications","volume":"285","author":"Luo","year":"2010","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib103","unstructured":"Gibbs, A., Tounge, B., Steele, R. NMR structure of an inhibitor bound dengue NS3 protease provides new insights into the NS2B NS3 ligand interactions."},{"key":"10.1016\/j.ejmech.2014.10.010_bib104","doi-asserted-by":"crossref","first-page":"2757","DOI":"10.1093\/emboj\/21.11.2757","article-title":"An RNA cap (nucleoside-2\u2032-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization","volume":"21","author":"Egloff","year":"2002","journal-title":"Embo J."},{"key":"10.1016\/j.ejmech.2014.10.010_bib105","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0012836","article-title":"Crystal structure of the dengue virus methyltransferase bound to a 5\u2032-capped octameric RNA","volume":"5","author":"Yap","year":"2010","journal-title":"Plos One"},{"key":"10.1016\/j.ejmech.2014.10.010_bib106","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1126\/science.1247749","article-title":"Flavivirus NS1 structures reveal surfaces for associations with membranes and the immune system","volume":"343","author":"Akey","year":"2014","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2014.10.010_bib107","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1016\/j.jmb.2008.11.026","article-title":"Structure of west nile virus NS3 protease: ligand stabilization of the catalytic conformation","volume":"385","author":"Robin","year":"2009","journal-title":"J.\u00a0Mol. Biol."},{"key":"10.1016\/j.ejmech.2014.10.010_bib108","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1110\/ps.072753207","article-title":"Structural evidence for regulation and specificity of flaviviral proteases and evolution of the flaviviridae fold","volume":"16","author":"Aleshin","year":"2007","journal-title":"Protein Sci."},{"key":"10.1016\/j.ejmech.2014.10.010_bib109","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.jmb.2007.06.055","article-title":"Crystal structure and activity of Kunjin virus NS3 helicase; protease and helicase domain assembly in the full length NS3 protein","volume":"372","author":"Mastrangelo","year":"2007","journal-title":"J.\u00a0Mol. Biol."},{"key":"10.1016\/j.ejmech.2014.10.010_bib110","unstructured":"Cheung, J., Franklin, M., Mancia, F., Rudolph, M., Cassidy, M., Gary, E., Burshteyn, F., Love, J. Structure of the Chikungunya virus nsP2 protease."},{"key":"10.1016\/j.ejmech.2014.10.010_bib111","unstructured":"Morin, B., Ferron, F.P., Malet, H., Coutard, B., Canard, B. Crystal structure of chikungunya virus NSp3 macrodomain in complex with a 2\u2032\u20135\u2032 oligoadenylate trimer."},{"key":"10.1016\/j.ejmech.2014.10.010_bib112","doi-asserted-by":"crossref","first-page":"7934","DOI":"10.1021\/jm901044z","article-title":"N-sulfonylanthranilic acid derivatives as allosteric inhibitors of dengue viral RNA-dependent RNA polymerase","volume":"52","author":"Yin","year":"2009","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2014.10.010_bib113","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0000356","article-title":"Discovery of a non-peptidic inhibitor of west nile virus NS3 protease by high-throughput docking","volume":"3","author":"Ekonomiuk","year":"2009","journal-title":"Plos Neglected Trop. Dis."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523414009362?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523414009362?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,9,28]],"date-time":"2018-09-28T14:56:09Z","timestamp":1538146569000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523414009362"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11]]},"references-count":113,"alternative-id":["S0223523414009362"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2014.10.010","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2014,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A perspective on targeting non-structural proteins to combat neglected tropical diseases: Dengue, West Nile and Chikungunya viruses","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2014.10.010","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2014 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}]}}