{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:37:23Z","timestamp":1790613443780,"version":"4.1.0"},"reference-count":66,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T00:00:00Z","timestamp":1656028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Late Sheikh Ibraheem Ahmed Azhar"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The Japanese encephalitis virus (JEV), a mosquito-borne flavivirus that causes viral encephalitis leading to neural damage, is a major threat in most Asian countries. The RNA-dependent RNA polymerase (RdRp) present in the viral genome is the key component for genome replication, making it an attractive target for antiviral drug development. In this study, the natural products from Echinacea angustifolia were retrieved for structure-based virtual screening against JEV\u2013RdRp. The top six compounds (Echinacoside, Echinacin, Rutin, Cynaroside, Quercetagetin 7-glucoside, and Kaempferol-3-glucoside) were obtained based on the highest negative docking score, ADMET (absorption, distribution, metabolism, excretion, and toxicity), and molecular interaction. The computational analysis of these selected compounds against the co-crystallized ligands, i.e., ATP and GTP, were performed. Further, 100 ns molecular dynamic simulation and post-free binding energy calculation of all the selected compounds complexed with JEV\u2013RdRP were performed to check the stability of the complexes. The obtained results showed considerable stability and intermolecular interaction with native ligand-binding site residues of JEV\u2013RdRp. Hence, selected natural compounds are admissible inhibitors of JEV\u2013RdRp protein and can be considered for future antiviral drug development studies.<\/jats:p>","DOI":"10.3390\/life12070952","type":"journal-article","created":{"date-parts":[[2022,6,26]],"date-time":"2022-06-26T21:01:41Z","timestamp":1656277301000},"page":"952","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Discovery of Small Molecules from Echinacea angustifolia Targeting RNA-Dependent RNA Polymerase of Japanese Encephalitis Virus"],"prefix":"10.3390","volume":"12","author":[{"given":"Pardeep","family":"Yadav","sequence":"first","affiliation":[{"name":"Department of Biotechnology, School of Engineering & Technology, Sharda University, Greater Noida 201310, India"},{"name":"Center for Bioinformatics, Computational and Systems Biology, Pathfinder Research and Training Foundation, Greater Noida 201308, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3667-7529","authenticated-orcid":false,"given":"Sherif A.","family":"El-Kafrawy","sequence":"additional","affiliation":[{"name":"Special Infectious Agents Unit-BSL-3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21362, Saudi Arabia"},{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21362, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3864-523X","authenticated-orcid":false,"given":"Mai M.","family":"El-Day","sequence":"additional","affiliation":[{"name":"Special Infectious Agents Unit-BSL-3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21362, Saudi Arabia"},{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21362, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1101-4155","authenticated-orcid":false,"given":"Wejdan T.","family":"Alghafari","sequence":"additional","affiliation":[{"name":"Special Infectious Agents Unit-BSL-3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21362, Saudi Arabia"},{"name":"Clinical Nutrition Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21362, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arwa A.","family":"Faizo","sequence":"additional","affiliation":[{"name":"Special Infectious Agents Unit-BSL-3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21362, Saudi Arabia"},{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21362, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7437-0755","authenticated-orcid":false,"given":"Saurabh Kumar","family":"Jha","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, School of Engineering & Technology, Sharda University, Greater Noida 201310, India"},{"name":"Department of Biotechnology Engineering and Food Technology, Chandigarh University, Mohali 140413, India"},{"name":"Department of Biotechnology, School of Applied & Life Sciences (SALS), Uttaranchal University, Dehradun 248007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0767-1328","authenticated-orcid":false,"given":"Vivek Dhar","family":"Dwivedi","sequence":"additional","affiliation":[{"name":"Center for Bioinformatics, Computational and Systems Biology, Pathfinder Research and Training Foundation, Greater Noida 201308, India"},{"name":"Institute of Advanced Materials, IAAM, 59053 Ulrika, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1736-181X","authenticated-orcid":false,"given":"Esam I.","family":"Azhar","sequence":"additional","affiliation":[{"name":"Special Infectious Agents Unit-BSL-3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21362, Saudi Arabia"},{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21362, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"242","DOI":"10.4269\/ajtmh.2001.65.242","article-title":"Phylogenetic analysis of Japanese encephalitis virus: Envelope gene based analysis reveals a fifth genotype, geographic clustering, and multiple introductions of the virus into the Indian subcontinent","volume":"65","author":"Uchil","year":"2001","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Li, M.H., Fu, S.H., Chen, W.X., Wang, H.Y., Guo, Y.H., Liu, Q.Y., Li, Y.X., Luo, H.M., Da, W., and Ji, D.Z.D. (2011). Genotype V Japanese Encephalitis Virus Is Emerging. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001231"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3091","DOI":"10.1128\/JVI.77.5.3091-3098.2003","article-title":"Origin and evolution of Japanese encephalitis virus in southeast Asia","volume":"77","author":"Solomon","year":"2003","journal-title":"J. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nrneurol.2018.30","article-title":"Japanese encephalitis\u2014The prospects for new treatments","volume":"14","author":"Turtle","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_5","first-page":"296","article-title":"Clinical manifestations of Japanese encephalitis in southern Taiwan","volume":"42","author":"Chen","year":"2009","journal-title":"J. Microbiol. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1093\/infdis\/167.5.1053","article-title":"Outbreak of Japanese encephalitis on the island of Saipan, 1990","volume":"167","author":"Paul","year":"1993","journal-title":"J. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/S0140-6736(05)78540-8","article-title":"Scourge of Japanese encephalitis in south-western Nepal","volume":"351","author":"Wakai","year":"1998","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.micinf.2011.01.002","article-title":"Japanese encephalitis virus: From genome to infectome","volume":"13","author":"Unni","year":"2011","journal-title":"Microbes Infect."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1136\/jnnp.68.4.405","article-title":"Japanese encephalitis","volume":"68","author":"Solomon","year":"2000","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"833701","DOI":"10.3389\/fcimb.2022.833701","article-title":"A Bibliometric Analysis of Global Research on Japanese Encephalitis From 1934 to 2020","volume":"12","author":"Xu","year":"2022","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_11","unstructured":"WHO (2021, September 30). Japanese Encephalitis. Available online: https:\/\/www.who.int\/en\/news-room\/fact-sheets\/detail\/japanese-encephalitis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"766","DOI":"10.2471\/BLT.10.085233","article-title":"Estimated global incidence of Japanese encephalitis: A systematic review","volume":"89","author":"Campbell","year":"2011","journal-title":"Bull. World Health Organ."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"263","DOI":"10.4161\/hv.26902","article-title":"Japanese encephalitis: The virus and vaccines","volume":"10","author":"Yun","year":"2014","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3203","DOI":"10.1021\/acs.jproteome.9b00318","article-title":"Analysis of the Zika and Japanese Encephalitis Virus NS5 Interactomes","volume":"18","author":"Kovanich","year":"2019","journal-title":"J. Proteome. Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kumar, S., Verma, A., Yadav, P., Dubey, S.K., Azhar, E.I., Maitra, S.S., and Dwivedi, V.D. (2022). Molecular pathogenesis of Japanese encephalitis and possible therapeutic strategies. Arch. Virol., 1\u201324.","DOI":"10.1007\/s00705-022-05481-z"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"19100","DOI":"10.1074\/jbc.270.32.19100","article-title":"Association between Ns3 and Ns5 Proteins of Dengue Virus Type-2 in the Putative Rna Replicase Is Linked to Differential Phosphorylation of Ns5","volume":"270","author":"Kapoor","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5451","DOI":"10.1128\/JVI.01982-05","article-title":"Nuclear localization of flavivirus RNA synthesis in infected cells","volume":"80","author":"Uchil","year":"2006","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.coviro.2014.09.011","article-title":"Regulation of Flavivirus RNA synthesis and replication","volume":"9","author":"Selisko","year":"2014","journal-title":"Curr. Opin. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0092-8674(00)81101-0","article-title":"The 1.85 angstrom structure of vaccinia protein VP39: A bifunctional enzyme that participates in the modification of both mRNA ends","volume":"85","author":"Hodel","year":"1996","journal-title":"Cell"},{"key":"ref_20","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":"ref_21","doi-asserted-by":"crossref","first-page":"e01294-19","DOI":"10.1128\/JVI.01294-19","article-title":"NS5 from Dengue Virus Serotype 2 Can Adopt a Conformation Analogous to That of Its Zika Virus and Japanese Encephalitis Virus Homologues","volume":"94","author":"Soh","year":"2019","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2758","DOI":"10.1093\/nar\/gkt1106","article-title":"RNA-dependent RNA polymerase of Japanese encephalitis virus binds the initiator nucleotide GTP to form a mechanistically important pre-initiation state","volume":"42","author":"Surana","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1056\/NEJM198809083191004","article-title":"Protection against Japanese encephalitis by inactivated vaccines","volume":"319","author":"Hoke","year":"1988","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"214","DOI":"10.4269\/ajtmh.1988.39.214","article-title":"Safety of a live-attenuated Japanese encephalitis virus vaccine (SA14-14-2) for children","volume":"39","author":"Xin","year":"1988","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Fan, Y.C., Chen, Y.Y., Chen, J.M., Huang, C., Huang, M., and Chiou, S.S. (2022). Effectiveness of Live-Attenuated Genotype III Japanese Encephalitis Viral Vaccine against Circulating Genotype I Viruses in Swine. Viruses, 14.","DOI":"10.3390\/v14010114"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ngwe Tun, M.M., Kyaw, A.K., Nwe, K.M., Inoue, S., Thant, K.Z., and Morita, K. (2021). Effectiveness of the SA 14-14-2 Live-Attenuated Japanese Encephalitis Vaccine in Myanmar. Vaccines, 9.","DOI":"10.3390\/vaccines9060568"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.jiph.2018.04.011","article-title":"Effectiveness of Japanese encephalitis SA 14-14-2 live attenuated vaccine among Indian children: Retrospective 1:4 matched case-control study","volume":"11","author":"Tandale","year":"2018","journal-title":"J. Infect. Public Health"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1016\/S0140-6736(96)91075-2","article-title":"Effectiveness of live-attenuated Japanese encephalitis vaccine (SA14-14-2): A case-control study","volume":"347","author":"Hennessy","year":"1996","journal-title":"Lancet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.imlet.2009.12.023","article-title":"Co-expression of Japanese encephalitis virus prM-E-NS1 antigen with granulocyte-macrophage colony-stimulating factor enhances humoral and anti-virus immunity after DNA vaccination","volume":"129","author":"Gao","year":"2010","journal-title":"Immunol. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3596","DOI":"10.1128\/JVI.76.8.3596-3604.2002","article-title":"Antiviral effects of an iminosugar derivative on flavivirus infections","volume":"76","author":"Wu","year":"2002","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1099\/vir.0.81123-0","article-title":"Antiviral effect of dehydroepiandrosterone on Japanese encephalitis virus infection","volume":"86","author":"Chang","year":"2005","journal-title":"J. Gen. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/1743-422X-5-64","article-title":"N-methylisatin-beta-thiosemicarbazone derivative (SCH 16) is an inhibitor of Japanese encephalitis virus infection in vitro and in vivo","volume":"5","author":"Sebastian","year":"2008","journal-title":"Virol. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"925830","DOI":"10.1155\/2012\/925830","article-title":"Antiviral Activity of Isatis indigotica Extract and Its Derived Indirubin against Japanese Encephalitis Virus","volume":"2012","author":"Chang","year":"2012","journal-title":"Evid.-Based Complement. Altern. Med"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e01055-17","DOI":"10.1128\/JVI.01055-17","article-title":"Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection","volume":"91","author":"Wang","year":"2017","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1099\/vir.0.18883-0","article-title":"Interference in Japanese encephalitis virus infection of Vero cells by a cationic amphiphilic drug, chlorpromazine","volume":"84","author":"Nawa","year":"2003","journal-title":"J. Gen. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1093\/infdis\/jiu179","article-title":"Etanercept reduces neuroinflammation and lethality in mous.se model of Japanese encephalitis","volume":"210","author":"Ye","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1111\/j.1471-4159.2008.05238.x","article-title":"Minocycline neuroprotects, reduces microglial activation, inhibits caspase 3 induction, and viral replication following Japanese encephalitis","volume":"105","author":"Mishra","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"18125","DOI":"10.1038\/s41598-021-96917-0","article-title":"Mechanistic insights into the Japanese encephalitis virus RNA dependent RNA polymerase protein inhibition by bioflavonoids from Azadirachta indica","volume":"11","author":"Dwivedi","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1080\/07391102.2020.1734485","article-title":"Anti-dengue infectivity evaluation of bioflavonoid from Azadirachta indica by dengue virus serine protease inhibition","volume":"39","author":"Dwivedi","year":"2021","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_40","first-page":"175","article-title":"In silico docking of quercetin-3-O-\u03b2-D-glucoside from Azadirachta indica with NS2B-NS3 protease in Dengue virus","volume":"19","author":"Dwivedi","year":"2018","journal-title":"Online J. Bioinform."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3447","DOI":"10.1002\/ptr.7039","article-title":"Medicinal plants: Treasure for antiviral drug discovery","volume":"35","author":"Ali","year":"2021","journal-title":"Phytother. Res. PTR"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s13337-015-0276-6","article-title":"Herbal plants and plant preparations as remedial approach for viral diseases","volume":"26","author":"Ganjhu","year":"2015","journal-title":"Virusdisease"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Nedyalkova, M., Vasighi, M., Sappati, S., Kumar, A., Madurga, S., and Simeonov, V. (2021). Inhibition Ability of Natural Compounds on Receptor-Binding Domain of SARS-CoV2: An In Silico Approach. Pharmaceuticals, 14.","DOI":"10.3390\/ph14121328"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"100043","DOI":"10.1016\/j.crphar.2021.100043","article-title":"Screening of phytoconstituents of Andrographis paniculata against various targets of Japanese encephalitis virus: An in-silico and in-vitro target-based approach","volume":"2","author":"Bhosale","year":"2021","journal-title":"Curr. Res. Pharmacol. Drug Discov."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1248\/bpb.19.1166","article-title":"Protective effect of astragali radix by oral administration against Japanese encephalitis virus infection in mice","volume":"19","author":"Kajimura","year":"1996","journal-title":"Biol. Pharm. Bull."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1093\/jac\/dkm503","article-title":"Novel strategy for treatment of Japanese encephalitis using arctigenin, a plant lignan","volume":"61","author":"Swarup","year":"2008","journal-title":"J. Antimicrob. Chemoth."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"16785","DOI":"10.3390\/ijms131216785","article-title":"Antiviral activity of baicalein and quercetin against the Japanese encephalitis virus","volume":"13","author":"Johari","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1211\/0022357056127","article-title":"Echinacea species (Echinacea angustifolia (DC.) Hell., Echinacea pallida (Nutt.) Nutt., Echinacea purpurea (L.) Moench): A review of their chemistry, pharmacology and clinical properties","volume":"57","author":"Barnes","year":"2005","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/s12985-020-01401-2","article-title":"In vitro virucidal activity of Echinaforce(R), an Echinacea purpurea preparation, against coronaviruses, including common cold coronavirus 229E and SARS-CoV-2","volume":"17","author":"Signer","year":"2020","journal-title":"Virol. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.aimed.2020.07.007","article-title":"The effect of quercetin on the prevention or treatment of COVID-19 and other respiratory tract infections in humans: A rapid review","volume":"7","author":"Aucoin","year":"2020","journal-title":"Adv. Integr. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.3390\/ph4071019","article-title":"Echinacea\u2014A Source of Potent Antivirals for Respiratory Virus Infections","volume":"4","author":"Hudson","year":"2011","journal-title":"Pharmaceuticals"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Bharadwaj, S., El-Kafrawy, S.A., Alandijany, T.A., Bajrai, L.H., Shah, A.A., Dubey, A., Sahoo, A.K., Yadava, U., Kamal, M.A., and Azhar, E.I. (2021). Structure-Based Identification of Natural Products as SARS-CoV-2 M(pro) Antagonist from Echinacea angustifolia Using Computational Approaches. Viruses, 13.","DOI":"10.3390\/v13020305"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"769896","DOI":"10.1155\/2012\/769896","article-title":"Applications of the phytomedicine Echinacea purpurea (Purple Coneflower) in infectious diseases","volume":"2012","author":"Hudson","year":"2012","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"D1388","DOI":"10.1093\/nar\/gkaa971","article-title":"PubChem in 2021: New data content and improved web interfaces","volume":"49","author":"Kim","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/978-1-4939-2269-7_19","article-title":"Small-molecule library screening by docking with PyRx","volume":"1263","author":"Dallakyan","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"113322","DOI":"10.1016\/j.molliq.2020.113322","article-title":"Density functional theory and molecular dynamics simulation support Ganoderma lucidum triterpenoids as broad range antagonist of matrix metalloproteinases","volume":"311","author":"Bharadwaj","year":"2020","journal-title":"J. Mol. Liq."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_60","unstructured":"(2020). Schr\u00f6dinger Release 2020-4, Maestro, Schr\u00f6dinger, LLC."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Bowers, K.J., Chow, D.E., Xu, H., Dror, R.O., Eastwood, M.P., Gregersen, B.A., Klepeis, J.L., Kolossvary, I., Moraes, M.A., and Sacerdoti, F.D. (2006, January 11\u201317). Scalable algorithms for molecular dynamics simulations on commodity clusters. Proceedings of the SC\u201906: Proceedings of the 2006 ACM\/IEEE Conference on Supercomputing, Tampa, FL, USA.","DOI":"10.1145\/1188455.1188544"},{"key":"ref_63","unstructured":"(2018). Schr\u00f6dinger Release 2018-4: Desmond Molecular Dynamics System, Maestro-Desmond Interoperability Tools, Schr\u00f6dinger."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1063\/1.463940","article-title":"Nose-Hoover Chains\u2014The Canonical Ensemble Via Continuous Dynamics","volume":"97","author":"Martyna","year":"1992","journal-title":"J. Chem. Phys."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/0010-4655(96)00016-1","article-title":"Ewald summation techniques in perspective: A survey","volume":"95","author":"Toukmaji","year":"1996","journal-title":"Comput. Phys. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.1093\/bioinformatics\/btl461","article-title":"Bio3d: An R package for the comparative analysis of protein structures","volume":"22","author":"Grant","year":"2006","journal-title":"Bioinformatics"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/7\/952\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:39:18Z","timestamp":1760139558000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/7\/952"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,24]]},"references-count":66,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["life12070952"],"URL":"https:\/\/doi.org\/10.3390\/life12070952","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,24]]}}}