{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T19:59:13Z","timestamp":1788897553530,"version":"build-2803163510"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2023,8,26]],"date-time":"2023-08-26T00:00:00Z","timestamp":1693008000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,8,26]],"date-time":"2023-08-26T00:00:00Z","timestamp":1693008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Manipal Academy of Higher Education, Manipal"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Divers"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Dengue is an emerging, mosquito-borne viral disease of international public health concern. Dengue is endemic in more than 100 countries across the world. However, there are no clinically approved antivirals for its cure. Drug repurposing proves to be an efficient alternative to conventional drug discovery approaches in this regard, as approved drugs with an established safety profile are tested for new indications, which circumvents several time-consuming experiments. In the present study, eight approved RNA-dependent RNA polymerase inhibitors of Hepatitis C virus were virtually screened against the Dengue virus polymerase protein, and their antiviral activity was assessed in vitro. Schr\u00f6dinger software was used for in silico screening, where the compounds were passed through several hierarchical filters. Among the eight compounds, dasabuvir was finally selected for in vitro cytotoxicity and antiviral screening. Cytotoxicity profiling of dasabuvir in Vero cells revealed changes in cellular morphology, cell aggregation, and detachment at 50\u00a0\u03bcM. Based on these results, four noncytotoxic concentrations of dasabuvir (0.1, 0.25, 0.5, and 1\u00a0\u00b5M) were selected for antiviral screening against DENV-2 under three experimental conditions: pre-infection, co-infection, and post-infection treatment, by plaque reduction assay. Viral plaques were reduced significantly (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) in the co-infection and post-infection treatment regimens; however, no reduction was observed in the pretreatment group. This indicated a possible interference of dasabuvir with NS5 RdRp, as seen from in silico interaction studies, translating into a reduction in virus plaques. Such studies reiterate the usefulness of drug repurposing as a viable strategy in antiviral drug discovery.<\/jats:p>\n                <jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>\n                <jats:p>In this drug repurposing study, dasabuvir, a known anti-hepatitis C drug, was selected through virtual screening and assessed for its anti-dengue activity.<\/jats:p>","DOI":"10.1007\/s11030-023-10716-5","type":"journal-article","created":{"date-parts":[[2023,8,26]],"date-time":"2023-08-26T09:02:30Z","timestamp":1693040550000},"page":"2831-2844","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Repurposing of approved antivirals against dengue virus serotypes: an in silico and in vitro mechanistic study"],"prefix":"10.1007","volume":"28","author":[{"given":"S. H.","family":"Rashmi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Sai","family":"Disha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Sudheesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Karunakaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Joseph","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anitha","family":"Jagadesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. P.","family":"Mudgal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,26]]},"reference":[{"key":"10716_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2012\/628475","volume":"2012","author":"MMF Alen","year":"2012","unstructured":"Alen MMF, Schols D (2012) Dengue virus entry as target for antiviral therapy. J Trop Med 2012:1\u201313. https:\/\/doi.org\/10.1155\/2012\/628475","journal-title":"J Trop Med"},{"key":"10716_CR2","unstructured":"World Health Organization (2009) Dengue guidelines for diagnosis, treatment, prevention and control\u202f: new edition"},{"key":"10716_CR3","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1038\/s41564-019-0476-8","volume":"4","author":"JP Messina","year":"2019","unstructured":"Messina JP, Brady OJ, Golding N et al (2019) The current and future global distribution and population at risk of dengue. Nat Microbiol 4:1508\u20131515. https:\/\/doi.org\/10.1038\/s41564-019-0476-8","journal-title":"Nat Microbiol"},{"key":"10716_CR4","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1038\/nature12060","volume":"496","author":"S Bhatt","year":"2013","unstructured":"Bhatt S, Gething PW, Brady OJ et al (2013) The global distribution and burden of dengue. Nature 496:504\u2013507. https:\/\/doi.org\/10.1038\/nature12060","journal-title":"Nature"},{"key":"10716_CR5","doi-asserted-by":"publisher","first-page":"b4338","DOI":"10.1136\/bmj.b4338","volume":"339","author":"MG Teixeira","year":"2009","unstructured":"Teixeira MG, Barreto ML (2009) Diagnosis and management of dengue. BMJ 339:b4338. https:\/\/doi.org\/10.1136\/bmj.b4338","journal-title":"BMJ"},{"key":"10716_CR6","doi-asserted-by":"publisher","first-page":"22","DOI":"10.4103\/2224-3151.206879","volume":"3","author":"D Cecilia","year":"2014","unstructured":"Cecilia D (2014) Current status of dengue and chikungunya in India. WHO South-East Asia J Public Health 3:22. https:\/\/doi.org\/10.4103\/2224-3151.206879","journal-title":"WHO South-East Asia J Public Health"},{"key":"10716_CR7","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1093\/infdis\/jis470","volume":"207","author":"NM Nguyen","year":"2013","unstructured":"Nguyen NM, Tran CNB, Phung LK et al (2013) A randomized, double-blind placebo controlled trial of balapiravir, a polymerase inhibitor, in adult dengue patients. J Infect Dis 207:1442\u20131450. https:\/\/doi.org\/10.1093\/infdis\/jis470","journal-title":"J Infect Dis"},{"key":"10716_CR8","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1016\/S1473-3099(14)70730-3","volume":"14","author":"JG Low","year":"2014","unstructured":"Low JG, Sung C, Wijaya L et al (2014) Efficacy and safety of celgosivir in patients with dengue fever (CELADEN): a phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial. Lancet Infect Dis 14:706\u2013715. https:\/\/doi.org\/10.1016\/S1473-3099(14)70730-3","journal-title":"Lancet Infect Dis"},{"key":"10716_CR9","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1007\/s00253-004-1783-3","volume":"66","author":"J Magden","year":"2005","unstructured":"Magden J, K\u00e4\u00e4ri\u00e4inen L, Ahola T (2005) Inhibitors of virus replication: recent developments and prospects. Appl Microbiol Biotechnol 66:612\u2013621. https:\/\/doi.org\/10.1007\/s00253-004-1783-3","journal-title":"Appl Microbiol Biotechnol"},{"key":"10716_CR10","doi-asserted-by":"publisher","first-page":"6","DOI":"10.21315\/mjms2018.25.5.2","volume":"25","author":"H Norazharuddin","year":"2018","unstructured":"Norazharuddin H, Lai NS (2018) Roles and prospects of dengue virus non-structural proteins as antiviral targets: an easy digest. Malays J Med Sci MJMS 25:6\u201315. https:\/\/doi.org\/10.21315\/mjms2018.25.5.2","journal-title":"Malays J Med Sci MJMS"},{"key":"10716_CR11","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.2174\/138945006779025383","volume":"7","author":"SM Rawlinson","year":"2006","unstructured":"Rawlinson SM, Pryor MJ, Wright PJ, Jans DA (2006) Dengue virus RNA polymerase NS5: A potential therapeutic target? Curr Drug Targets 7:1623\u20131638. https:\/\/doi.org\/10.2174\/138945006779025383","journal-title":"Curr Drug Targets"},{"key":"10716_CR12","doi-asserted-by":"publisher","first-page":"91","DOI":"10.3390\/v9040091","volume":"9","author":"A El Sahili","year":"2017","unstructured":"El Sahili A, Lescar J (2017) Dengue Virus Non-Structural Protein 5. Viruses 9:91. https:\/\/doi.org\/10.3390\/v9040091","journal-title":"Viruses"},{"key":"10716_CR13","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.antiviral.2015.04.010","volume":"119","author":"SP Lim","year":"2015","unstructured":"Lim SP, Noble CG, Shi P-Y (2015) The dengue virus NS5 protein as a target for drug discovery. Antiviral Res 119:57\u201367. https:\/\/doi.org\/10.1016\/j.antiviral.2015.04.010","journal-title":"Antiviral Res"},{"key":"10716_CR14","doi-asserted-by":"publisher","first-page":"14362","DOI":"10.1074\/jbc.M110.214189","volume":"286","author":"G Zou","year":"2011","unstructured":"Zou G, Chen Y-L, Dong H et al (2011) Functional analysis of two cavities in flavivirus NS5 polymerase. J Biol Chem 286:14362\u201314372. https:\/\/doi.org\/10.1074\/jbc.M110.214189","journal-title":"J Biol Chem"},{"key":"10716_CR15","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.antiviral.2009.11.009","volume":"87","author":"M Bollati","year":"2010","unstructured":"Bollati M, Alvarez K, Assenberg R et al (2010) Structure and functionality in flavivirus NS-proteins: perspectives for drug design. Antiviral Res 87:125\u2013148. https:\/\/doi.org\/10.1016\/j.antiviral.2009.11.009","journal-title":"Antiviral Res"},{"key":"10716_CR16","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1208\/s12248-012-9390-1","volume":"14","author":"TI Oprea","year":"2012","unstructured":"Oprea TI, Mestres J (2012) Drug repurposing: far beyond new targets for old drugs. AAPS J 14:759\u2013763. https:\/\/doi.org\/10.1208\/s12248-012-9390-1","journal-title":"AAPS J"},{"key":"10716_CR17","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.tips.2013.11.006","volume":"35","author":"Z Lou","year":"2014","unstructured":"Lou Z, Sun Y, Rao Z (2014) Current progress in antiviral strategies. Trends Pharmacol Sci 35:86\u2013102. https:\/\/doi.org\/10.1016\/j.tips.2013.11.006","journal-title":"Trends Pharmacol Sci"},{"key":"10716_CR18","doi-asserted-by":"publisher","first-page":"205873842110026","DOI":"10.1177\/20587384211002621","volume":"35","author":"S Kausar","year":"2021","unstructured":"Kausar S, Said Khan F, RehmanM IMU et al (2021) A review: mechanism of action of antiviral drugs. Int J Immunopathol Pharmacol 35:20587384211002620. https:\/\/doi.org\/10.1177\/20587384211002621","journal-title":"Int J Immunopathol Pharmacol"},{"key":"10716_CR19","doi-asserted-by":"publisher","first-page":"53","DOI":"10.2217\/fvl.13.121","volume":"9","author":"S Potisopon","year":"2014","unstructured":"Potisopon S, Priet S, Selisko B, Canard B (2014) Comparison of dengue virus and HCV: from impact on global health to their RNA-dependent RNA polymerases. Future Virol 9:53\u201367. https:\/\/doi.org\/10.2217\/fvl.13.121","journal-title":"Future Virol"},{"key":"10716_CR20","doi-asserted-by":"publisher","first-page":"599","DOI":"10.3390\/microorganisms8040599","volume":"8","author":"M Stefanik","year":"2020","unstructured":"Stefanik M, Valdes JJ, Ezebuo FC et al (2020) FDA-Approved drugs efavirenz, tipranavir, and dasabuvir inhibit replication of multiple flaviviruses in vero cells. Microorganisms 8:599. https:\/\/doi.org\/10.3390\/microorganisms8040599","journal-title":"Microorganisms"},{"key":"10716_CR21","doi-asserted-by":"publisher","first-page":"144","DOI":"10.3390\/ijms17020144","volume":"17","author":"X Du","year":"2016","unstructured":"Du X, Li Y, Xia Y-L et al (2016) Insights into protein-ligand interactions: mechanisms, models, and methods. Int J Mol Sci 17:144. https:\/\/doi.org\/10.3390\/ijms17020144","journal-title":"Int J Mol Sci"},{"key":"10716_CR22","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","volume":"27","author":"G Madhavi Sastry","year":"2013","unstructured":"Madhavi Sastry G, Adzhigirey M, Day T et al (2013) Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J Comput Aided Mol Des 27:221\u2013234. https:\/\/doi.org\/10.1007\/s10822-013-9644-8","journal-title":"J Comput Aided Mol Des"},{"key":"10716_CR23","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1021\/acs.jctc.5b00864","volume":"12","author":"E Harder","year":"2016","unstructured":"Harder E, Damm W, Maple J et al (2016) OPLS3: A force field providing broad coverage of drug-like small molecules and proteins. J Chem Theory Comput 12:281\u2013296. https:\/\/doi.org\/10.1021\/acs.jctc.5b00864","journal-title":"J Chem Theory Comput"},{"key":"10716_CR24","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1021\/jm0306430","volume":"47","author":"RA Friesner","year":"2004","unstructured":"Friesner RA, Banks JL, Murphy RB et al (2004) Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem 47:1739\u20131749. https:\/\/doi.org\/10.1021\/jm0306430","journal-title":"J Med Chem"},{"key":"10716_CR25","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1021\/jm030644s","volume":"47","author":"TA Halgren","year":"2004","unstructured":"Halgren TA, Murphy RB, Friesner RA et al (2004) Glide: a new approach for rapid, accurate docking and scoring. 2. enrichment factors in database screening. J Med Chem 47:1750\u20131759. https:\/\/doi.org\/10.1021\/jm030644s","journal-title":"J Med Chem"},{"key":"10716_CR26","doi-asserted-by":"publisher","first-page":"6177","DOI":"10.1021\/jm051256o","volume":"49","author":"RA Friesner","year":"2006","unstructured":"Friesner RA, Murphy RB, Repasky MP et al (2006) Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein\u2212ligand complexes. J Med Chem 49:6177\u20136196. https:\/\/doi.org\/10.1021\/jm051256o","journal-title":"J Med Chem"},{"key":"10716_CR27","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1021\/jm050540c","volume":"49","author":"W Sherman","year":"2006","unstructured":"Sherman W, Day T, Jacobson MP et al (2006) Novel procedure for modeling ligand\/receptor induced fit effects. J Med Chem 49:534\u2013553. https:\/\/doi.org\/10.1021\/jm050540c","journal-title":"J Med Chem"},{"key":"10716_CR28","doi-asserted-by":"publisher","first-page":"151","DOI":"10.3390\/v9060151","volume":"9","author":"E Abdurakhmanov","year":"2017","unstructured":"Abdurakhmanov E, \u00d8ie Solbak S, Danielson U (2017) Biophysical mode-of-action and selectivity analysis of allosteric inhibitors of hepatitis C virus (HCV) polymerase. Viruses 9:151. https:\/\/doi.org\/10.3390\/v9060151","journal-title":"Viruses"},{"key":"10716_CR29","first-page":"673","volume":"15","author":"SK Krishnan","year":"2011","unstructured":"Krishnan SK, Ganguly S, Veerasamy R, Jan B (2011) Synthesis, antiviral and cytotoxic investigation of 2-phenyl-3-substituted quinazolin-4(3H)-ones. Eur Rev Med Pharmacol Sci 15:673\u2013681","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"10716_CR30","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/S0378-8741(97)00152-9","volume":"60","author":"SJ Semple","year":"1998","unstructured":"Semple SJ, Reynolds GD, O\u2019Leary MC, Flower RLP (1998) Screening of Australian medicinal plants for antiviral activity. J Ethnopharmacol 60:163\u2013172. https:\/\/doi.org\/10.1016\/S0378-8741(97)00152-9","journal-title":"J Ethnopharmacol"},{"key":"10716_CR31","doi-asserted-by":"publisher","first-page":"ftaa032","DOI":"10.1093\/femspd\/ftaa032","volume":"78","author":"K Sd","year":"2020","unstructured":"K. SD, Puranik R, N. S, et al (2020) Structure-based identification of small molecules against influenza a virus endonuclease: an in silico and in vitro approach. Pathog Dis 78:ftaa032. https:\/\/doi.org\/10.1093\/femspd\/ftaa032","journal-title":"Pathog Dis"},{"key":"10716_CR32","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1186\/s12985-017-0895-1","volume":"14","author":"SA Abdul Ahmad","year":"2017","unstructured":"Abdul Ahmad SA, Palanisamy UD, Tejo BA et al (2017) Geraniin extracted from the rind of Nephelium lappaceum binds to dengue virus type-2 envelope protein and inhibits early stage of virus replication. Virol J 14:229. https:\/\/doi.org\/10.1186\/s12985-017-0895-1","journal-title":"Virol J"},{"key":"10716_CR33","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.antiviral.2015.07.010","volume":"122","author":"Y-L Chen","year":"2015","unstructured":"Chen Y-L, Yokokawa F, Shi P-Y (2015) The search for nucleoside\/nucleotide analog inhibitors of dengue virus. Antiviral Res 122:12\u201319. https:\/\/doi.org\/10.1016\/j.antiviral.2015.07.010","journal-title":"Antiviral Res"},{"key":"10716_CR34","doi-asserted-by":"publisher","first-page":"28766","DOI":"10.1074\/jbc.M500588200","volume":"280","author":"J Li","year":"2005","unstructured":"Li J, Lim SP, Beer D et al (2005) Functional profiling of recombinant ns3 proteases from all four serotypes of dengue virus using tetrapeptide and octapeptide substrate libraries *. J Biol Chem 280:28766\u201328774. https:\/\/doi.org\/10.1074\/jbc.M500588200","journal-title":"J Biol Chem"},{"key":"10716_CR35","doi-asserted-by":"publisher","first-page":"6345","DOI":"10.1038\/s41598-017-06612-2","volume":"7","author":"H-T Xu","year":"2017","unstructured":"Xu H-T, Colby-Germinario SP, Hassounah SA et al (2017) Evaluation of Sofosbuvir (\u03b2-D-2\u2032-deoxy-2\u2032-\u03b1-fluoro-2\u2032-\u03b2-C-methyluridine) as an inhibitor of dengue virus replication #. Sci Rep 7:6345. https:\/\/doi.org\/10.1038\/s41598-017-06612-2","journal-title":"Sci Rep"},{"key":"10716_CR36","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1128\/AAC.18.1.125","volume":"18","author":"WC Koff","year":"1980","unstructured":"Koff WC, Elm JL, Halstead SB (1980) Inhibition of dengue virus replication by amantadine hydrochloride. Antimicrob Agents Chemother 18:125\u2013129","journal-title":"Antimicrob Agents Chemother"},{"key":"10716_CR37","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.2174\/156802607780906753","volume":"7","author":"CN Cavasotto","year":"2007","unstructured":"Cavasotto CN, W. Orry AJ, (2007) Ligand docking and structure-based virtual screening in drug discovery. Curr Top Med Chem 7:1006\u20131014. https:\/\/doi.org\/10.2174\/156802607780906753","journal-title":"Curr Top Med Chem"},{"key":"10716_CR38","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/nrd1468","volume":"3","author":"TT Ashburn","year":"2004","unstructured":"Ashburn TT, Thor KB (2004) Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov 3:673\u2013683. https:\/\/doi.org\/10.1038\/nrd1468","journal-title":"Nat Rev Drug Discov"},{"key":"10716_CR39","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/978-1-4939-8955-3_2","volume-title":"Computational Methods for Drug Repurposing","author":"F Sohraby","year":"2019","unstructured":"Sohraby F, Bagheri M, Aryapour H (2019) Performing an In Silico Repurposing of Existing Drugs by Combining Virtual Screening and Molecular Dynamics Simulation. In: Vanhaelen Q (ed) Computational Methods for Drug Repurposing. Springer, New York, pp 23\u201343"},{"key":"10716_CR40","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1007\/978-1-4939-7201-2_18","volume-title":"Proteomics for Drug Discovery: Methods and Protocols","author":"M Kontoyianni","year":"2017","unstructured":"Kontoyianni M (2017) Docking and Virtual Screening in Drug Discovery. In: Lazar IM, Kontoyianni M, Lazar AC (eds) Proteomics for Drug Discovery: Methods and Protocols. Springer, New York, pp 255\u2013266"},{"key":"10716_CR41","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1002\/wsbm.1337","volume":"8","author":"RA Hodos","year":"2016","unstructured":"Hodos RA, Kidd BA, Shameer K et al (2016) In silico methods for drug repurposing and pharmacology. WIREs Syst Biol Med 8:186\u2013210. https:\/\/doi.org\/10.1002\/wsbm.1337","journal-title":"WIREs Syst Biol Med"},{"key":"10716_CR42","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/S1359-6446(05)03484-7","volume":"10","author":"M Congreve","year":"2005","unstructured":"Congreve M, Murray CW, Blundell TL (2005) Keynote review: Structural biology and drug discovery. Drug Discov Today 10:895\u2013907. https:\/\/doi.org\/10.1016\/S1359-6446(05)03484-7","journal-title":"Drug Discov Today"},{"key":"10716_CR43","doi-asserted-by":"publisher","first-page":"1970","DOI":"10.1039\/C7MD00381A","volume":"8","author":"RF de Freitas","year":"2017","unstructured":"de Freitas RF, Schapira M (2017) A systematic analysis of atomic protein\u2013ligand interactions in the PDB. MedChemComm 8:1970\u20131981. https:\/\/doi.org\/10.1039\/C7MD00381A","journal-title":"MedChemComm"},{"key":"10716_CR44","doi-asserted-by":"publisher","first-page":"3747","DOI":"10.1016\/j.bmcl.2012.04.017","volume":"22","author":"Y Liu","year":"2012","unstructured":"Liu Y, Lim BH, Jiang WW et al (2012) Identification of aryl dihydrouracil derivatives as palm initiation site inhibitors of HCV NS5B polymerase. Bioorg Med Chem Lett 22:3747\u20133750. https:\/\/doi.org\/10.1016\/j.bmcl.2012.04.017","journal-title":"Bioorg Med Chem Lett"},{"key":"10716_CR45","doi-asserted-by":"publisher","first-page":"e5068","DOI":"10.7717\/peerj.5068","volume":"6","author":"NB Nncube","year":"2018","unstructured":"Nncube NB, Ramharack P, Soliman MES (2018) Using bioinformatics tools for the discovery of Dengue RNA-dependent RNA polymerase inhibitors. PeerJ 6:e5068. https:\/\/doi.org\/10.7717\/peerj.5068","journal-title":"PeerJ"},{"key":"10716_CR46","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1128\/AAC.04619-14","volume":"59","author":"W Kati","year":"2015","unstructured":"Kati W, Koev G, Irvin M et al (2015) In vitro activity and resistance profile of dasabuvir, a nonnucleoside hepatitis C virus polymerase inhibitor. Antimicrob Agents Chemother 59:1505\u20131511. https:\/\/doi.org\/10.1128\/AAC.04619-14","journal-title":"Antimicrob Agents Chemother"},{"key":"10716_CR47","unstructured":"Anonymous (2018) Exviera. In: Eur. Med. Agency. https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/exviera. Accessed 10 Feb 2020"},{"key":"10716_CR48","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1080\/17460441.2017.1322955","volume":"12","author":"M El Kassas","year":"2017","unstructured":"El Kassas M, Elbaz T, Hafez E et al (2017) Discovery and preclinical development of dasabuvir for the treatment of hepatitis C infection. Expert Opin Drug Discov 12:635\u2013642. https:\/\/doi.org\/10.1080\/17460441.2017.1322955","journal-title":"Expert Opin Drug Discov"},{"key":"10716_CR49","doi-asserted-by":"publisher","first-page":"204020661880758","DOI":"10.1177\/2040206618807580","volume":"26","author":"EJ Franco","year":"2018","unstructured":"Franco EJ, Rodriquez JL, Pomeroy JJ et al (2018) The effectiveness of antiviral agents with broad-spectrum activity against chikungunya virus varies between host cell lines. Antivir Chem Chemother 26:2040206618807580. https:\/\/doi.org\/10.1177\/2040206618807580","journal-title":"Antivir Chem Chemother"},{"key":"10716_CR50","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1099\/vir.0.017954-0","volume":"91","author":"SRP Kumar","year":"2010","unstructured":"Kumar SRP, Patil JA, Cecilia D et al (2010) Evolution, dispersal and replacement of American genotype dengue type 2 viruses in India (1956\u20132005): selection pressure and molecular clock analyses. J Gen Virol 91:707\u2013720. https:\/\/doi.org\/10.1099\/vir.0.017954-0","journal-title":"J Gen Virol"},{"key":"10716_CR51","unstructured":"Anoop M, Issac A, Mathew T, et al (2010) Genetic characterization of dengue virus serotypes causing concurrent infection in an outbreak in Ernakulam, Kerala, South India. IJEB Vol4808 August 2010"},{"key":"10716_CR52","first-page":"373","volume":"136","author":"N Gupta","year":"2012","unstructured":"Gupta N, Srivastava S, Jain A, Chaturvedi UC (2012) Dengue in India. Indian J Med Res 136:373\u2013390","journal-title":"Indian J Med Res"},{"key":"10716_CR53","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1016\/j.bbrc.2013.05.130","volume":"436","author":"PK Dash","year":"2013","unstructured":"Dash PK, Sharma S, Soni M et al (2013) Complete genome sequencing and evolutionary analysis of Indian isolates of dengue virus type 2. Biochem Biophys Res Commun 436:478\u2013485. https:\/\/doi.org\/10.1016\/j.bbrc.2013.05.130","journal-title":"Biochem Biophys Res Commun"},{"key":"10716_CR54","doi-asserted-by":"publisher","first-page":"e617","DOI":"10.1371\/journal.pntd.0000617","volume":"4","author":"JR Fried","year":"2010","unstructured":"Fried JR, Gibbons RV, Kalayanarooj S et al (2010) Serotype-specific differences in the risk of dengue hemorrhagic fever: an analysis of data collected in Bangkok, Thailand from 1994 to 2006. PLoS Negl Trop Dis 4:e617. https:\/\/doi.org\/10.1371\/journal.pntd.0000617","journal-title":"PLoS Negl Trop Dis"},{"key":"10716_CR55","doi-asserted-by":"publisher","first-page":"3016","DOI":"10.3390\/molecules26103016","volume":"26","author":"K Panda","year":"2021","unstructured":"Panda K, Alagarasu K, Patil P et al (2021) In vitro antiviral activity of \u03b1-mangostin against dengue virus serotype-2 (DENV-2). Molecules 26:3016. https:\/\/doi.org\/10.3390\/molecules26103016","journal-title":"Molecules"},{"key":"10716_CR56","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.01440","author":"D Yi","year":"2020","unstructured":"Yi D, Li Q, Pang L et al (2020) Identification of a broad-spectrum viral inhibitor targeting a novel allosteric site in the RNA-dependent RNA polymerases of dengue virus and norovirus. Front Microbiol. https:\/\/doi.org\/10.3389\/fmicb.2020.01440","journal-title":"Front Microbiol"},{"key":"10716_CR57","doi-asserted-by":"publisher","first-page":"8541","DOI":"10.1074\/jbc.M115.710731","volume":"291","author":"CG Noble","year":"2016","unstructured":"Noble CG, Lim SP, Arora R et al (2016) A conserved pocket in the dengue virus polymerase identified through fragment-based screening *. J Biol Chem 291:8541\u20138548. https:\/\/doi.org\/10.1074\/jbc.M115.710731","journal-title":"J Biol Chem"},{"key":"10716_CR58","doi-asserted-by":"publisher","first-page":"e1005737","DOI":"10.1371\/journal.ppat.1005737","volume":"12","author":"SP Lim","year":"2016","unstructured":"Lim SP, Noble CG, Seh CC et al (2016) Potent allosteric dengue virus NS5 polymerase inhibitors: mechanism of action and resistance profiling. PLOS Pathog 12:e1005737. https:\/\/doi.org\/10.1371\/journal.ppat.1005737","journal-title":"PLOS Pathog"},{"key":"10716_CR59","doi-asserted-by":"publisher","first-page":"4753","DOI":"10.1128\/jvi.02283-06","volume":"81","author":"TL Yap","year":"2007","unstructured":"Yap TL, Xu T, Chen Y-L et al (2007) Crystal structure of the dengue virus RNA-dependent RNA polymerase catalytic domain at 1.85-angstrom resolution. J Virol 81:4753\u20134765. https:\/\/doi.org\/10.1128\/jvi.02283-06","journal-title":"J Virol"},{"key":"10716_CR60","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.antiviral.2010.11.002","volume":"89","author":"J Chang","year":"2011","unstructured":"Chang J, Schul W, Butters TD et al (2011) Combination of \u03b1-glucosidase inhibitor and ribavirin for the treatment of dengue virus infection in vitro and in vivo. Antiviral Res 89:26\u201334. https:\/\/doi.org\/10.1016\/j.antiviral.2010.11.002","journal-title":"Antiviral Res"},{"key":"10716_CR61","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1080\/14756366.2017.1355791","volume":"32","author":"S Pelliccia","year":"2017","unstructured":"Pelliccia S, Wu Y-H, Coluccia A et al (2017) Inhibition of dengue virus replication by novel inhibitors of RNA-dependent RNA polymerase and protease activities. J Enzyme Inhib Med Chem 32:1091\u20131101. https:\/\/doi.org\/10.1080\/14756366.2017.1355791","journal-title":"J Enzyme Inhib Med Chem"},{"key":"10716_CR62","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1038\/nchembio817","volume":"2","author":"JB Fitzgerald","year":"2006","unstructured":"Fitzgerald JB, Schoeberl B, Nielsen UB, Sorger PK (2006) Systems biology and combination therapy in the quest for clinical efficacy. Nat Chem Biol 2:458\u2013466. https:\/\/doi.org\/10.1038\/nchembio817","journal-title":"Nat Chem Biol"}],"updated-by":[{"DOI":"10.1007\/s11030-023-10748-x","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T00:00:00Z","timestamp":1700784000000}}],"container-title":["Molecular Diversity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11030-023-10716-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11030-023-10716-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11030-023-10716-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T14:22:39Z","timestamp":1733149359000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11030-023-10716-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,26]]},"references-count":62,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10716"],"URL":"https:\/\/doi.org\/10.1007\/s11030-023-10716-5","relation":{"correction":[{"id-type":"doi","id":"10.1007\/s11030-023-10748-x","asserted-by":"object"}]},"ISSN":["1381-1991","1573-501X"],"issn-type":[{"value":"1381-1991","type":"print"},{"value":"1573-501X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,26]]},"assertion":[{"value":"3 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 August 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 August 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 November 2023","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s11030-023-10748-x","URL":"https:\/\/doi.org\/10.1007\/s11030-023-10748-x","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no competing interests to declare that are relevant to the content of this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}