{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T03:39:04Z","timestamp":1764733144507,"version":"3.46.0"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"CSIR, New Delhi","award":["09\/0844(18476)\/2024-EMR-I"],"award-info":[{"award-number":["09\/0844(18476)\/2024-EMR-I"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Comput Aided Mol Des"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1007\/s10822-025-00720-2","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T03:33:41Z","timestamp":1764732821000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Virtual reality and cheminformatics-driven discovery of a potential broad-spectrum natural antagonist against flaviviral methyltransferases and its cytotoxicity evaluation"],"prefix":"10.1007","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6362-318X","authenticated-orcid":false,"given":"Jobin","family":"Thomas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2845-8115","authenticated-orcid":false,"given":"Rajendra","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1971-4778","authenticated-orcid":false,"given":"Jitendra","family":"Satija","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"720_CR1","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1021\/acsinfecdis.2c00571","volume":"9","author":"SK Samrat","year":"2023","unstructured":"Samrat SK, Bashir Q, Huang Y, Trieshmann CW, Tharappel AM, Zhang R, Chen K, Zheng YG, Li Z, Li H (2023) Broad-spectrum small-molecule inhibitors targeting the SAM-binding site of flavivirus NS5 methyltransferase. ACS Infect Dis 9:1319\u20131333. https:\/\/doi.org\/10.1021\/acsinfecdis.2c00571","journal-title":"ACS Infect Dis"},{"key":"720_CR2","doi-asserted-by":"publisher","first-page":"1458166","DOI":"10.3389\/fmicb.2024.1458166","volume":"15","author":"Y Liang","year":"2024","unstructured":"Liang Y, Dai X (2024) The global incidence and trends of three common flavivirus infections (Dengue, yellow fever, and Zika) from 2011 to 2021. Front Microbiol 15:1458166. https:\/\/doi.org\/10.3389\/fmicb.2024.1458166","journal-title":"Front Microbiol"},{"key":"720_CR3","doi-asserted-by":"publisher","first-page":"152057","DOI":"10.1016\/j.bbrc.2025.152057","volume":"775","author":"V Loaiza-Cano","year":"2025","unstructured":"Loaiza-Cano V, Pardo-Rodriguez D, V\u00e1zquez CA, Restrepo MP, Burgos JC, Avila JS, Gallo FN, Dellarole M, Cordo SM, Garc\u00eda CC, Galeano E, Zapata W, Ruiz-Saenz J, Martinez-Gutierrez M (2025) Antiviral in vitro activity of a novel dichlorinated tyrosine Methyl ester derivative against the infection of two flaviviruses of public health concern, dengue and Zika virus. Biochem Biophys Res Commun 775:152057. https:\/\/doi.org\/10.1016\/j.bbrc.2025.152057","journal-title":"Biochem Biophys Res Commun"},{"key":"720_CR4","doi-asserted-by":"publisher","first-page":"6233","DOI":"10.1074\/jbc.M110.179184","volume":"286","author":"SP Lim","year":"2011","unstructured":"Lim SP, Sonntag LS, Noble C, Nilar SH, Ng RH, Zou G, Monaghan P, Chung KY, Dong H, Liu B, Bodenreider C, Lee G, Ding M, Chan WL, Wang G, Jian YL, Chao AT, Lescar J, Yin Z, Vedananda TR, Keller TH, Shi PY (2011) Small molecule inhibitors that selectively block dengue virus methyltransferase. J Biol Chem 286:6233\u20136240. https:\/\/doi.org\/10.1074\/jbc.M110.179184","journal-title":"J Biol Chem"},{"key":"720_CR5","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.1080\/21645515.2019.1658503","volume":"15","author":"SJ Thomas","year":"2019","unstructured":"Thomas SJ, Yoon IK (2019) A review of Dengvaxia\u00ae: development to deployment. Hum Vaccin Immunother 15:2295\u20132314. https:\/\/doi.org\/10.1080\/21645515.2019.1658503","journal-title":"Hum Vaccin Immunother"},{"key":"720_CR6","doi-asserted-by":"publisher","first-page":"145","DOI":"10.3390\/vaccines13020145","volume":"13","author":"H Mwandumba","year":"2025","unstructured":"Mwandumba H, Choong See K (2025) Dengue vaccination: a practical guide for clinicians. Vaccines 13:145. https:\/\/doi.org\/10.3390\/vaccines13020145","journal-title":"Vaccines"},{"key":"720_CR7","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1002\/JMV.25646","volume":"92","author":"S Nasar","year":"2020","unstructured":"Nasar S, Rashid N, Iftikhar S (2020) Dengue proteins with their role in pathogenesis, and strategies for developing an effective anti-dengue treatment: a review. J Med Virol 92:941\u2013955. https:\/\/doi.org\/10.1002\/JMV.25646","journal-title":"J Med Virol"},{"key":"720_CR8","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/s13567-021-00966-2","volume":"52","author":"X Zhang","year":"2021","unstructured":"Zhang X, Zhang Y, Jia R, Wang M, Yin Z, Cheng A (2021) Structure and function of capsid protein in flavivirus infection and its applications in the development of vaccines and therapeutics. Vet Res 52:98. https:\/\/doi.org\/10.1186\/s13567-021-00966-2","journal-title":"Vet Res"},{"key":"720_CR9","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/j.virs.2025.05.009","volume":"40","author":"X Zhu","year":"2025","unstructured":"Zhu X, Gao X, Wu Y, Lu J, Chen X, Zhao C, Li H, Zhang Z, Liu S, Xiao G, Pan X (2025) Eltrombopag, an FDA-approved drug, inhibits dengue virus type 2 by targeting NS2B-NS3 protease. Virol Sin 40:439\u2013450. https:\/\/doi.org\/10.1016\/j.virs.2025.05.009","journal-title":"Virol Sin"},{"key":"720_CR10","doi-asserted-by":"publisher","first-page":"283","DOI":"10.3390\/ph18030283","volume":"18","author":"L Ivanova","year":"2025","unstructured":"Ivanova L, Naumenko K, Varjak M, Koit S, Morozovsky Y, Merits A, Karelson M, Zusinaite E (2025) Dengue virus inhibitors as potential broad-spectrum flavivirus inhibitors. Pharmaceuticals 18:283. https:\/\/doi.org\/10.3390\/ph18030283","journal-title":"Pharmaceuticals"},{"key":"720_CR11","doi-asserted-by":"publisher","first-page":"e202304932","DOI":"10.1002\/slct.202304932","volume":"9","author":"J Thomas","year":"2024","unstructured":"Thomas J, Satija J (2024) Cheminformatics and QSAR-based identification of natural bioactive compounds as potent inhibitors of SARS\u2010CoV\u20102\u00a0N\u20107 methyltransferases. ChemistrySelect 9:e202304932. https:\/\/doi.org\/10.1002\/slct.202304932","journal-title":"ChemistrySelect"},{"key":"720_CR12","doi-asserted-by":"publisher","first-page":"14762","DOI":"10.1038\/ncomms14762","volume":"8","author":"B Zhao","year":"2017","unstructured":"Zhao B, Yi G, Du F, Chuang YC, Vaughan RC, Sankaran B, Kao CC, Li P (2017) Structure and function of the Zika virus full-length NS5 protein. Nat Commun 8:14762. https:\/\/doi.org\/10.1038\/ncomms14762","journal-title":"Nat Commun"},{"key":"720_CR13","doi-asserted-by":"publisher","first-page":"e0130062","DOI":"10.1371\/journal.pone.0130062","volume":"10","author":"M Brecher","year":"2015","unstructured":"Brecher M, Chen H, Liu B, Banavali NK, Jones SA, Zhang J, Li Z, Kramer LD, Li H (2015) Novel broad spectrum inhibitors targeting the flavivirus methyltransferase. PLoS ONE 10:e0130062. https:\/\/doi.org\/10.1371\/journal.pone.0130062","journal-title":"PLoS ONE"},{"key":"720_CR14","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.antiviral.2014.03.013","volume":"106","author":"B Coutard","year":"2014","unstructured":"Coutard B, Decroly E, Li C, Sharff A, Lescar J, Bricogne G, Barral K (2014) Assessment of dengue virus helicase and methyltransferase as targets for fragment-based drug discovery. Antiviral Res 106:61\u201370. https:\/\/doi.org\/10.1016\/j.antiviral.2014.03.013","journal-title":"Antiviral Res"},{"key":"720_CR15","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1039\/d2ra04836a","volume":"13","author":"A Ullah","year":"2022","unstructured":"Ullah A, Atia-Tul-Wahab N, Gong P, Khan AM, Choudhary MI (2022) Identification of new inhibitors of NS5 from dengue virus using saturation transfer difference (STD-NMR) and molecular Docking studies. RSC Adv 13:355\u2013369. https:\/\/doi.org\/10.1039\/d2ra04836a","journal-title":"RSC Adv"},{"key":"720_CR16","doi-asserted-by":"publisher","first-page":"665379","DOI":"10.3389\/fcimb.2021.665379","volume":"11","author":"W Song","year":"2021","unstructured":"Song W, Zhang H, Zhang Y, Chen Y, Lin Y, Han Y, Jiang J (2021) Identification and characterization of Zika virus NS5 methyltransferase inhibitors. Front Cell Infect Microbiol 11:665379. https:\/\/doi.org\/10.3389\/fcimb.2021.665379","journal-title":"Front Cell Infect Microbiol"},{"key":"720_CR17","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1002\/1873-3468.70054","volume":"599","author":"M Bhutkar","year":"2025","unstructured":"Bhutkar M, Kumar A, Rani R, Singh V, Saha A, Pathak A, Kothiala A, Mahajan S, Waghmode B, Verma S, Kumar R, Mudgal R, Sircar D, Kumar P, Tomar S (2025) Structure-based identification of Herbacetin and caffeic acid phenethyl ester as inhibitors of S-adenosylmethionine-dependent viral methyltransferase. FEBS Lett 599:1531\u20131555. https:\/\/doi.org\/10.1002\/1873-3468.70054","journal-title":"FEBS Lett"},{"key":"720_CR18","doi-asserted-by":"publisher","first-page":"2437","DOI":"10.3390\/ijms25042437","volume":"25","author":"D Fiorucci","year":"2024","unstructured":"Fiorucci D, Meaccini M, Poli G, Stincarelli MA, Vagaggini C, Giannecchini S, Sutto-Ortiz P, Canard B, Decroly E, Dreassi E, Brai A, Botta M (2024) Identification of novel non-nucleoside inhibitors of Zika virus NS5 protein targeting MTase activity. Int J Mol Sci 25:2437. https:\/\/doi.org\/10.3390\/ijms25042437","journal-title":"Int J Mol Sci"},{"key":"720_CR19","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1021\/acsinfecdis.5b00070","volume":"1","author":"M Brecher","year":"2016","unstructured":"Brecher M, Chen H, Li Z, Banavali NK, Jones SA, Zhang J, Kramer LD, Li H (2016) Identification and characterization of novel broad-spectrum inhibitors of the flavivirus methyltransferase. ACS Infect Dis 1:340\u2013349. https:\/\/doi.org\/10.1021\/acsinfecdis.5b00070","journal-title":"ACS Infect Dis"},{"key":"720_CR20","doi-asserted-by":"publisher","first-page":"7870","DOI":"10.1038\/s41598-023-33341-6","volume":"13","author":"R Shukla","year":"2023","unstructured":"Shukla R, Chandra A, Kumar A, Kandpal P, Avashthi H, Goel VK, Qamar I, Singh N, Kelvin DJ, Singh TR (2023) Repurposing of drugs against methyltransferase as potential Zika virus therapies. Sci Rep 13:7870. https:\/\/doi.org\/10.1038\/s41598-023-33341-6","journal-title":"Sci Rep"},{"key":"720_CR21","doi-asserted-by":"publisher","first-page":"8147","DOI":"10.1038\/s41598-023-35192-7","volume":"13","author":"P Jain","year":"2023","unstructured":"Jain P, Satija J, Sudandiradoss C (2023) Discovery of Andrographolide hit analog as a potent cyclooxygenase-2 inhibitor through consensus MD-simulation, electrostatic potential energy simulation and ligand efficiency metrics. Sci Rep 13:8147. https:\/\/doi.org\/10.1038\/s41598-023-35192-7","journal-title":"Sci Rep"},{"key":"720_CR22","doi-asserted-by":"publisher","first-page":"1189786","DOI":"10.3389\/fmicb.2023.1189786","volume":"14","author":"S Akash","year":"2023","unstructured":"Akash S, Bay\u0131l I, Rahman MA, Mukerjee N, Maitra S, Islam MR, Rajkhowa S, Ghosh A, Al-Hussain SA, Zaki MEA, Jaiswal V, Sah S, Barboza JJ, Sah R (2023) Target specific Inhibition of West nile virus envelope glycoprotein and methyltransferase using phytocompounds: an in Silico strategy leveraging molecular Docking and dynamics simulation. Front Microbiol 14:1189786. https:\/\/doi.org\/10.3389\/fmicb.2023.1189786","journal-title":"Front Microbiol"},{"key":"720_CR23","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1111\/1462-2920.15400","volume":"23","author":"J Zhu","year":"2021","unstructured":"Zhu J, Song S, Sun Z, Lian L, Shi L, Ren A, Zhao M (2021) Regulation of glutamine synthetase activity by transcriptional and posttranslational modifications negatively influences Ganoderic acid biosynthesis in ganoderma lucidum. Environ Microbiol 23:1286\u20131297. https:\/\/doi.org\/10.1111\/1462-2920.15400","journal-title":"Environ Microbiol"},{"key":"720_CR24","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1186\/1743-422X-8-560","volume":"8","author":"K Zandi","year":"2011","unstructured":"Zandi K, Teoh BT, Sam SS, Wong PF, Mustafa M, Abubakar S (2011) Antiviral activity of four types of bioflavonoid against dengue virus type-2. Virol J 8:560. https:\/\/doi.org\/10.1186\/1743-422X-8-560","journal-title":"Virol J"},{"key":"720_CR25","doi-asserted-by":"publisher","first-page":"184241","DOI":"10.1155\/2015\/184241","volume":"2015","author":"Y Abba","year":"2015","unstructured":"Abba Y, Hassim H, Hamzah H, Noordin MM (2015) Antiviral activity of Resveratrol against human and animal viruses. Adv Virol 2015:184241. https:\/\/doi.org\/10.1155\/2015\/184241","journal-title":"Adv Virol"},{"key":"720_CR26","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1093\/nar\/28.1.235","volume":"28","author":"HM Berman","year":"2000","unstructured":"Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The protein data bank. Nucleic Acids Res 28:235\u2013242. https:\/\/doi.org\/10.1093\/nar\/28.1.235","journal-title":"Nucleic Acids Res"},{"key":"720_CR27","doi-asserted-by":"publisher","first-page":"14830","DOI":"10.18632\/oncotarget.14780","volume":"8","author":"H Zhou","year":"2017","unstructured":"Zhou H, Wang F, Wang H, Chen C, Zhang T, Han X, Wang D, Chen C, Wu C, Xie W, Wang Z, Zhang L, Wang L, Yang H, Zhou H, Wang F, Wang H, Chen C, Zhang T, Han X, Wang D, Chen C, Wu C, Xie W, Wang Z, Zhang L, Wang L, Yang H (2017) The conformational changes of Zika virus methyltransferase upon converting SAM to SAH. Oncotarget 8:14830\u201314834. https:\/\/doi.org\/10.18632\/oncotarget.14780","journal-title":"Oncotarget"},{"key":"720_CR28","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.antiviral.2014.09.003","volume":"111","author":"CG Noble","year":"2014","unstructured":"Noble CG, Li SH, Dong H, Chew SH, Shi PY (2014) Crystal structure of dengue virus methyltransferase without S-adenosyl-L-methionine. Antiviral Res 111:78\u201381. https:\/\/doi.org\/10.1016\/j.antiviral.2014.09.003","journal-title":"Antiviral Res"},{"key":"720_CR29","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1007\/978-1-4939-7366-8_4","volume":"1685","author":"H Land","year":"2018","unstructured":"Land H, Humble MS (2018) YASARA: A tool to obtain structural guidance in biocatalytic investigations. Methods Mol Biol 1685:43\u201367. https:\/\/doi.org\/10.1007\/978-1-4939-7366-8_4","journal-title":"Methods Mol Biol"},{"key":"720_CR30","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/1758-2946-3-33","volume":"3","author":"NM O\u2019Boyle","year":"2011","unstructured":"O\u2019Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR (2011) Open babel: an open chemical toolbox. J Cheminform 3:33. https:\/\/doi.org\/10.1186\/1758-2946-3-33","journal-title":"J Cheminform"},{"key":"720_CR31","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"O Trott","year":"2010","unstructured":"Trott O, Olson AJ (2010) AutoDock vina: improving the speed and accuracy of Docking with a new scoring function, efficient optimization and multithreading. J Comput Chem 31:455. https:\/\/doi.org\/10.1002\/jcc.21334","journal-title":"J Comput Chem"},{"key":"720_CR32","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1080\/07391102.2023.2206287","volume":"42","author":"J Thomas","year":"2023","unstructured":"Thomas J, Kumar S, Satija J (2023) Integrated molecular and quantum mechanical approach to identify novel potent natural bioactive compound against 2\u2032-O-methyltransferase (nsp16) of SARS-CoV-2. J Biomol Struct Dyn 42:1999\u20132012. https:\/\/doi.org\/10.1080\/07391102.2023.2206287","journal-title":"J Biomol Struct Dyn"},{"key":"720_CR33","doi-asserted-by":"publisher","first-page":"107532","DOI":"10.1016\/j.jmgm.2020.107532","volume":"96","author":"L Masters","year":"2020","unstructured":"Masters L, Eagon S, Heying M (2020) Evaluation of consensus scoring methods for AutoDock Vina, Smina and Idock. J Mol Graph Model 96:107532. https:\/\/doi.org\/10.1016\/j.jmgm.2020.107532","journal-title":"J Mol Graph Model"},{"key":"720_CR34","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/jcc.20084","volume":"25","author":"EF Pettersen","year":"2004","unstructured":"Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera\u2013a visualization system for exploratory research and analysis. J Comput Chem 25:1605\u20131612. https:\/\/doi.org\/10.1002\/jcc.20084","journal-title":"J Comput Chem"},{"key":"720_CR35","doi-asserted-by":"publisher","first-page":"W513","DOI":"10.1093\/nar\/gkae303","volume":"52","author":"P Banerjee","year":"2024","unstructured":"Banerjee P, Kemmler E, Dunkel M, Preissner R (2024) ProTox 3.0: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res 52:W513\u2013W520. https:\/\/doi.org\/10.1093\/nar\/gkae303","journal-title":"Nucleic Acids Res"},{"key":"720_CR36","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","volume":"1\u20132","author":"MJ Abraham","year":"2015","unstructured":"Abraham MJ, Murtola T, Schulz R, P\u00e1ll S, Smith JC, Hess B, Lindah E (2015) GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1\u20132:19\u201325. https:\/\/doi.org\/10.1016\/j.softx.2015.06.001","journal-title":"SoftwareX"},{"key":"720_CR37","doi-asserted-by":"publisher","first-page":"9801","DOI":"10.1038\/s41598-024-58532-7","volume":"14","author":"J Thomas","year":"2024","unstructured":"Thomas J, Ghosh A, Ranjan S, Satija J (2024) Cheminformatics approach to identify Andrographolide derivatives as dual inhibitors of methyltransferases (nsp14 and nsp16) of SARS-CoV-2. Sci Rep 14:9801. https:\/\/doi.org\/10.1038\/s41598-024-58532-7","journal-title":"Sci Rep"},{"key":"720_CR38","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1007\/s11030-023-10667-x","volume":"28","author":"J Kumar","year":"2023","unstructured":"Kumar J, Shankar G, Kumar S, Thomas J, Singh N, Srikrishna S (2023) Extraction, isolation, synthesis, and biological evaluation of novel piperic acid derivatives for the treatment of alzheimer\u2019s disease. Mol Divers 28:1439\u20131458. https:\/\/doi.org\/10.1007\/s11030-023-10667-x","journal-title":"Mol Divers"},{"key":"720_CR39","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1007\/s11030-023-10717-4","volume":"28","author":"G Singh","year":"2023","unstructured":"Singh G, Thomas J, Wadhawa S, Kashyap A, Rahaman SA, Borkotoky S, Datta A, Singh GK, Mishra I, Rai G, Satija J, Dubey VK, Modi G (2023) Repurposing the in-house generated alzheimer\u2019s disease targeting molecules through computational and preliminary in-vitro studies for the management of SARS-coronavirus-2. Mol Divers 28:2847\u20132862. https:\/\/doi.org\/10.1007\/s11030-023-10717-4","journal-title":"Mol Divers"},{"key":"720_CR40","doi-asserted-by":"publisher","first-page":"9954","DOI":"10.1021\/jp003020w","volume":"105","author":"P Mark","year":"2001","unstructured":"Mark P, Nilsson L (2001) Structure and dynamics of the TIP3P, SPC, and SPC\/E water models at 298 K. J Phys Chem A 105:9954\u20139960. https:\/\/doi.org\/10.1021\/jp003020w","journal-title":"J Phys Chem A"},{"key":"720_CR41","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/nmeth.4067","volume":"14","author":"J Huang","year":"2016","unstructured":"Huang J, Rauscher S, Nawrocki G, Ran T, Feig M, De Groot BL, Grubm\u00fcller H, MacKerell AD (2016) CHARMM36m: an improved force field for folded and intrinsically disordered proteins. Nat Methods 14:71\u201373. https:\/\/doi.org\/10.1038\/nmeth.4067","journal-title":"Nat Methods"},{"key":"720_CR42","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1016\/j.ijbiomac.2018.12.124","volume":"126","author":"A Sonkar","year":"2019","unstructured":"Sonkar A, Shukla H, Shukla R, Kalita J, Tripathi T (2019) Unfolding of acinetobacter baumannii MurA proceeds through a metastable intermediate: a combined spectroscopic and computational investigation. Int J Biol Macromol 126:941\u2013951. https:\/\/doi.org\/10.1016\/j.ijbiomac.2018.12.124","journal-title":"Int J Biol Macromol"},{"key":"720_CR43","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.jmgm.2019.06.008","volume":"91","author":"R Shukla","year":"2019","unstructured":"Shukla R, Munjal NS, Singh TR (2019) Identification of novel small molecules against GSK3\u03b2 for alzheimer\u2019s disease using chemoinformatics approach. J Mol Graph Model 91:91\u2013104. https:\/\/doi.org\/10.1016\/j.jmgm.2019.06.008","journal-title":"J Mol Graph Model"},{"key":"720_CR44","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-658-0_11","volume-title":"Protein dynamics, methods in molecular biology","author":"CC David","year":"2014","unstructured":"David CC, Jacobs DJ (2014) Principal component analysis: a method for determining the essential dynamics of proteins. In: Livesay D (ed) Protein dynamics, methods in molecular biology, 1st edn. Humana, Totowa, NJ. https:\/\/doi.org\/10.1007\/978-1-62703-658-0_11","edition":"1"},{"key":"720_CR45","doi-asserted-by":"publisher","first-page":"6281","DOI":"10.1021\/acs.jctc.1c00645","volume":"17","author":"MS Vald\u00e9s-Tresanco","year":"2021","unstructured":"Vald\u00e9s-Tresanco MS, Vald\u00e9s-Tresanco ME, Valiente PA, Moreno E (2021) Gmx_MMPBSA: a new tool to perform end-state free energy calculations with GROMACS. J Chem Theory Comput 17:6281\u20136291. https:\/\/doi.org\/10.1021\/acs.jctc.1c00645","journal-title":"J Chem Theory Comput"},{"key":"720_CR46","doi-asserted-by":"publisher","first-page":"e202500559","DOI":"10.1002\/slct.202500559","volume":"10","author":"A Prasad","year":"2025","unstructured":"Prasad A, Thomas J, Bhatt S, Ghosh A, Ranjan S, Satija J (2025) Andrographolide derivative as therapeutic lead against mutated \u03b2-lactamase enzyme: an in-silico approach to combat AMR. ChemistrySelect 10:e202500559. https:\/\/doi.org\/10.1002\/slct.202500559","journal-title":"ChemistrySelect"},{"key":"720_CR47","unstructured":"Dennington R, Keith TA, Millam JM, Semichem Inc, Mission S, KS (2016) GaussView, Version 6.1"},{"key":"720_CR48","unstructured":"Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Petersson GA, Nakatsuji H, Li X, Caricato M, Marenich AV, Bloino J, Janesko BG, Gomperts R, Mennucci B, Hratchian HP (2016) V J Gaussian 16, Revision C.01"},{"key":"720_CR49","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1021\/ci800293n","volume":"49","author":"KE Hevener","year":"2009","unstructured":"Hevener KE, Zhao W, Ball DM, Babaoglu K, Qi J, White SW, Lee RE (2009) Validation of molecular Docking programs for virtual screening against dihydropteroate synthase. J Chem Inf Model 49:444. https:\/\/doi.org\/10.1021\/ci800293n","journal-title":"J Chem Inf Model"},{"key":"720_CR50","doi-asserted-by":"publisher","first-page":"19410","DOI":"10.1074\/jbc.M800613200","volume":"283","author":"H Kroschewski","year":"2008","unstructured":"Kroschewski H, Siew PL, Butcher RE, Yap TL, Lescar J, Wright PJ, Vasudevan SG, Davidson AD (2008) Mutagenesis of the dengue virus type 2 NS5 methyltransferase domain. J Biol Chem 283:19410\u201319421. https:\/\/doi.org\/10.1074\/jbc.M800613200","journal-title":"J Biol Chem"},{"key":"720_CR51","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1002\/jcc.20566","volume":"28","author":"IS Moreira","year":"2007","unstructured":"Moreira IS, Fernandes PA, Ramos MJ (2007) Computational Alanine scanning mutagenesis\u2014an improved methodological approach. J Comput Chem 28:644\u2013654. https:\/\/doi.org\/10.1002\/jcc.20566","journal-title":"J Comput Chem"},{"key":"720_CR52","doi-asserted-by":"publisher","first-page":"2150","DOI":"10.3390\/v14102150","volume":"14","author":"M Punekar","year":"2022","unstructured":"Punekar M, Kasabe B, Patil P, Kakade MB, Parashar D, Alagarasu K, Cherian S (2022) A transcriptomics-based bioinformatics approach for identification and in vitro screening of FDA-approved drugs for repurposing against dengue virus-2. Viruses 14:2150. https:\/\/doi.org\/10.3390\/v14102150","journal-title":"Viruses"},{"key":"720_CR53","doi-asserted-by":"publisher","first-page":"102868","DOI":"10.1016\/j.jksus.2023.102868","volume":"35","author":"R Marimuthu Ragavan","year":"2023","unstructured":"Marimuthu Ragavan R, Purushothaman I, Swaminathan R, Almutairi SM, Hussein DS, Rasheed RA, Narasingam A (2023) Malacitanolide, Reissantin E and Paclitaxel compounds as inhibitors of envelope, NS5 and NS2B\/NS3 target proteins of dengue virus: computational Docking and molecular dynamics simulations studies. J King Saud Univ - Sci 35:102868. https:\/\/doi.org\/10.1016\/j.jksus.2023.102868","journal-title":"J King Saud Univ - Sci"},{"key":"720_CR54","doi-asserted-by":"publisher","first-page":"e1006411","DOI":"10.1371\/journal.ppat.1006411","volume":"13","author":"M Brecher","year":"2017","unstructured":"Brecher M, Li Z, Liu B, Zhang J, Koetzner CA, Alifarag A, Jones SA, Lin O, Kramer LD, Li H (2017) A conformational switch high-throughput screening assay and allosteric Inhibition of the flavivirus NS2B-NS3 protease. PLOS Pathog 13:e1006411. https:\/\/doi.org\/10.1371\/journal.ppat.1006411","journal-title":"PLOS Pathog"},{"key":"720_CR55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/S41426-018-0191-1","volume":"7","author":"CF Yang","year":"2018","unstructured":"Yang CF, Gopula B, Liang JJ, Li JK, Chem SY, Lee YL, Chen CS, Lin YL (2018) Novel AR-12 derivatives, P12-23 and P12-34, inhibit flavivirus replication by blocking host de Novo pyrimidine biosynthesis. Emerg Microbes Infect 7:1\u201311. https:\/\/doi.org\/10.1038\/S41426-018-0191-1","journal-title":"Emerg Microbes Infect"},{"key":"720_CR56","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1016\/j.virs.2024.09.001","volume":"39","author":"L Huang","year":"2024","unstructured":"Huang L, Liu L, Zhu J, Chen N, Chen J, Chan CF, Gao F, Yin Y, Sun J, Zhang R, Zhang K, Qi W, Yue J (2024) Bis-benzylisoquinoline alkaloids inhibit flavivirus entry and replication by compromising endolysosomal trafficking and autophagy. Virol Sin 39:892\u2013908. https:\/\/doi.org\/10.1016\/j.virs.2024.09.001","journal-title":"Virol Sin"},{"key":"720_CR57","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.antiviral.2017.09.004","volume":"146","author":"N Mumtaz","year":"2017","unstructured":"Mumtaz N, Jimmerson LC, Bushman LR, Kiser JJ, Aron G, Reusken CBEM, Koopmans MPG, Kampen JJAV (2017) Cell-line dependent antiviral activity of Sofosbuvir against Zika virus. Antiviral Res 146:161\u2013163. https:\/\/doi.org\/10.1016\/j.antiviral.2017.09.004","journal-title":"Antiviral Res"},{"key":"720_CR58","doi-asserted-by":"publisher","first-page":"16348","DOI":"10.1038\/s41598-019-52626-3","volume":"9","author":"AHD Cataneo","year":"2019","unstructured":"Cataneo AHD, Kuczera D, Koishi AC, Zanluca C, Silveira GF, de Arruda TB, Suzukawa AA, Bortot LO, Dias-Baruffi M, Verri WA Jr., Robert AW, Stimamiglio MA, dos Santos CND, Wowk PF, Bordignon J (2019) The citrus flavonoid naringenin impairs the in vitro infection of human cells by Zika virus. Sci Rep 9:16348. https:\/\/doi.org\/10.1038\/s41598-019-52626-3","journal-title":"Sci Rep"},{"key":"720_CR59","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1039\/D3OB01861J","volume":"22","author":"M Pacetti","year":"2024","unstructured":"Pacetti M, Pismataro MC, Felicetti T, Giammarino F, Bonomini A, Tiecco M, Bertagnin C, Barreca ML, Germani R, Cecchetti V, Vicenti I, Tabarrini O, Zazzi M, Loregian A, Massari S (2024) Switching the three-component Biginelli-like reaction conditions for the regioselective synthesis of new 2-amino[1,2,4]triazolo[1,5-a]pyrimidines. Org Biomol Chem 22:767\u2013783. https:\/\/doi.org\/10.1039\/D3OB01861J","journal-title":"Org Biomol Chem"}],"container-title":["Journal of Computer-Aided Molecular Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10822-025-00720-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10822-025-00720-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10822-025-00720-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T03:33:43Z","timestamp":1764732823000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10822-025-00720-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,3]]},"references-count":59,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["720"],"URL":"https:\/\/doi.org\/10.1007\/s10822-025-00720-2","relation":{},"ISSN":["0920-654X","1573-4951"],"issn-type":[{"value":"0920-654X","type":"print"},{"value":"1573-4951","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,3]]},"assertion":[{"value":"4 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"14"}}