{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:16:40Z","timestamp":1787498200616,"version":"build-2736575974"},"reference-count":53,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"LOEWE-Center DRUID (Novel Drug Targets against Poverty-related and Neglected Tropical In-fectious Diseases)","award":["FlexFunds"],"award-info":[{"award-number":["FlexFunds"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["Projektnummer 197785619 \u2013 SFB 1021"],"award-info":[{"award-number":["Projektnummer 197785619 \u2013 SFB 1021"]}]},{"name":"Foundation for Research of Natural Resources in Finland, Marjatta ja Eino Kollin S\u00e4\u00e4ti\u00f6","award":["Jari Yli-Kauhaluoma"],"award-info":[{"award-number":["Jari Yli-Kauhaluoma"]}]},{"name":"COST Action","award":["CM-0801 (New drugs for neglected diseases)"],"award-info":[{"award-number":["CM-0801 (New drugs for neglected diseases)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The hepatic bile acid transporter Na+\/taurocholate co-transporting polypeptide (NTCP) was identified in 2012 as the high-affinity hepatic receptor for the hepatitis B and D viruses (HBV\/HDV). Since then, this carrier has emerged as promising drug target for HBV\/HDV virus entry inhibitors, but the synthetic peptide Hepcludex\u00ae of high molecular weight is the only approved HDV entry inhibitor so far. The present study aimed to identify small molecules as novel NTCP inhibitors with anti-viral activity. A ligand-based bioinformatic approach was used to generate and validate appropriate pharmacophore and QSAR (quantitative structure\u2013activity relationship) models. Half-maximal inhibitory concentrations (IC50) for binding inhibition of the HBV\/HDV-derived preS1 peptide (as surrogate parameter for virus binding to NTCP) were determined in NTCP-expressing HEK293 cells for 150 compounds of different chemical classes. IC50 values ranged from 2 \u00b5M up to &gt;1000 \u00b5M. The generated pharmacophore and QSAR models were used for virtual screening of drug-like chemicals from the ZINC15 database (~11 million compounds). The 20 best-performing compounds were then experimentally tested for preS1-peptide binding inhibition in NTCP-HEK293 cells. Among them, four compounds were active and revealed experimental IC50 values for preS1-peptide binding inhibition of 9, 19, 20, and 35 \u00b5M, which were comparable to the QSAR-based predictions. All these compounds also significantly inhibited in vitro HDV infection of NTCP-HepG2 cells, without showing any cytotoxicity. The best-performing compound in all assays was ZINC000253533654. In conclusion, the present study demonstrates that virtual compound screening based on NTCP-specific pharmacophore and QSAR models can predict novel active hit compounds for the development of HBV\/HDV entry inhibitors.<\/jats:p>","DOI":"10.3390\/v13081489","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T21:21:21Z","timestamp":1627593681000},"page":"1489","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Identification of Novel HBV\/HDV Entry Inhibitors by Pharmacophore- and QSAR-Guided Virtual Screening"],"prefix":"10.3390","volume":"13","author":[{"given":"Michael","family":"Kirstgen","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5429-0088","authenticated-orcid":false,"given":"Simon Franz","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kira Alessandra Alicia Theresa","family":"Lowjaga","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Goldmann","sequence":"additional","affiliation":[{"name":"Institute of Medical Virology, National Reference Center for Hepatitis B Viruses and Hepatitis D Viruses, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0259-0062","authenticated-orcid":false,"given":"Felix","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Institute of Medical Virology, National Reference Center for Hepatitis B Viruses and Hepatitis D Viruses, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami","family":"Alakurtti","sequence":"additional","affiliation":[{"name":"Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, FI-00014 Helsinki, Finland"},{"name":"VTT Technical Research Centre of Finland, Biologinkuja 7, FI-02044 Espoo, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0370-7653","authenticated-orcid":false,"given":"Jari","family":"Yli-Kauhaluoma","sequence":"additional","affiliation":[{"name":"Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, FI-00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Heinz","family":"Baringhaus","sequence":"additional","affiliation":[{"name":"Sanofi-Aventis Deutschland GmbH, 65926 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reimar","family":"Krieg","sequence":"additional","affiliation":[{"name":"Institute of Anatomy II, University Hospital Jena, Teichgraben 7, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5039-0252","authenticated-orcid":false,"given":"Dieter","family":"Glebe","sequence":"additional","affiliation":[{"name":"Institute of Medical Virology, National Reference Center for Hepatitis B Viruses and Hepatitis D Viruses, Justus Liebig University Giessen, 35392 Giessen, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2663-1858","authenticated-orcid":false,"given":"Joachim","family":"Geyer","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,29]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2017). Global Hepatitis Report 2017, WHO. Geneva 2017. Licence:CC BY-NC-SA 3.0 IGO."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1055\/s-0033-1345717","article-title":"The molecular virology of hepatitis B virus","volume":"33","author":"Glebe","year":"2013","journal-title":"Semin. Liver. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1053\/j.gastro.2005.03.090","article-title":"Mapping of the hepatitis B virus attachment site by use of infection-inhibiting preS1 lipopeptides and tupaia hepatocytes","volume":"129","author":"Glebe","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1128\/JVI.79.3.1613-1622.2005","article-title":"Efficient inhibition of hepatitis B virus infection by acylated peptides derived from the large viral surface protein","volume":"79","author":"Gripon","year":"2005","journal-title":"J. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0140-6736(10)61931-9","article-title":"Hepatitis delta virus","volume":"378","author":"Hughes","year":"2011","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/liv.14364","article-title":"Can we cure hepatitis B virus with novel direct-acting antivirals?","volume":"40","author":"Martinez","year":"2020","journal-title":"Liver Int."},{"key":"ref_7","unstructured":"World Health Organization (2015). Guidelines for the Prevention, Care and Treatment of Persons with Chronic Hepatitis b Infection, WHO."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Yan, H., Zhong, G., Xu, G., He, W., Jing, Z., Gao, Z., Huang, Y., Qi, Y., Peng, B., and Wang, H. (2012). Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. eLife, 1.","DOI":"10.7554\/eLife.00049"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/j.jhep.2014.05.018","article-title":"Kinetics of the bile acid transporter and hepatitis B virus receptor Na+\/taurocholate cotransporting polypeptide (NTCP) in hepatocytes","volume":"61","author":"Mohr","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_10","unstructured":"(2021, May 15). MYR Pharmaceuticals. Available online: http:\/\/myr-pharma.com\/."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"112959","DOI":"10.1016\/j.jpba.2019.112959","article-title":"Development of a mass spectrometric screening assay for hepatitis B virus entry inhibitors","volume":"178","author":"Goh","year":"2020","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.bbrc.2013.12.052","article-title":"Evaluation and identification of hepatitis B virus entry inhibitors using HepG2 cells overexpressing a membrane transporter NTCP","volume":"443","author":"Iwamoto","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"21772","DOI":"10.1038\/s41598-020-78618-2","article-title":"Selective hepatitis B and D virus entry inhibitors from the group of pentacyclic lupane-type betulin-derived triterpenoids","volume":"10","author":"Kirstgen","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kirstgen, M., Lowjaga, K.A.A.T., M\u00fcller, S.F., Goldmann, N., Lehmann, F., Glebe, D., Baringhaus, K.-H., and Geyer, J. (2021). Hepatitis D Virus Entry Inhibitors Based on Repurposing Intestinal Bile Acid Reabsorption Inhibitors. Viruses, 13.","DOI":"10.3390\/v13040666"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1002\/cmdc.201100510","article-title":"Discovery of 2-(2-benzoxazoyl amino)-4-aryl-5-cyanopyrimidine as negative allosteric modulators (NAMs) of metabotropic glutamate receptor 5 (mGlu(5)): From an artificial neural network virtual screen to an in vivo tool compound","volume":"7","author":"Mueller","year":"2012","journal-title":"ChemMedChem"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.cbpa.2010.03.020","article-title":"Apparent activity in high-throughput screening: Origins of compound-dependent assay interference","volume":"14","author":"Thorne","year":"2010","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"735","DOI":"10.3390\/molecules18010735","article-title":"Benchmarking ligand-based virtual High-Throughput Screening with the PubChem database","volume":"18","author":"Butkiewicz","year":"2013","journal-title":"Molecules"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1021\/ja01062a035","article-title":"p-\u03c3-\u03c0 Analysis. A Method for the Correlation of Biological Activity and Chemical Structure","volume":"86","author":"Hansch","year":"1964","journal-title":"J. Am. Chem. Soc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4977","DOI":"10.1021\/jm4004285","article-title":"QSAR modeling: Where have you been? Where are you going to?","volume":"57","author":"Cherkasov","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1021\/acs.jcim.5b00559","article-title":"ZINC 15-Ligand Discovery for Everyone","volume":"55","author":"Sterling","year":"2015","journal-title":"J. Chem. Inf. Model."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1517\/17460441.2013.761204","article-title":"How far can virtual screening take us in drug discovery?","volume":"8","author":"Kar","year":"2013","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.3389\/fphar.2018.01275","article-title":"QSAR-Based Virtual Screening: Advances and Applications in Drug Discovery","volume":"9","author":"Neves","year":"2018","journal-title":"Front Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"19728","DOI":"10.1074\/jbc.M702663200","article-title":"Cloning and functional characterization of human sodium-dependent organic anion transporter (SLC10A6)","volume":"282","author":"Geyer","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Grosser, G., M\u00fcller, S.F., Kirstgen, M., D\u00f6ring, B., and Geyer, J. (2021). Substrate Specificities and Inhibition Pattern of the Solute Carrier Family 10 Members NTCP, ASBT and SOAT. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.689757"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"17007","DOI":"10.1073\/pnas.1908072116","article-title":"Highly diversified shrew hepatitis B viruses corroborate ancient origins and divergent infection patterns of mammalian hepadnaviruses","volume":"116","author":"Rasche","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/j.jhep.2018.01.029","article-title":"A novel hepatitis B virus species discovered in capuchin monkeys sheds new light on the evolution of primate hepadnaviruses","volume":"68","author":"Konig","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"M\u00fcller, S.F., K\u00f6nig, A., D\u00f6ring, B., Glebe, D., and Geyer, J. (2018). Characterisation of the hepatitis B virus cross-species transmission pattern via Na+\/taurocholate co-transporting polypeptides from 11 New World and Old World primate species. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0199200"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1016\/j.bmc.2010.01.003","article-title":"Synthesis and anti-leishmanial activity of heterocyclic betulin derivatives","volume":"18","author":"Alakurtti","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1021\/np9003245","article-title":"Betulin-derived compounds as inhibitors of alphavirus replication","volume":"72","author":"Pohjala","year":"2009","journal-title":"J. Nat. Prod."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1016\/j.bcp.2010.06.051","article-title":"Inhibitory effect of the natural product betulin and its derivatives against the intracellular bacterium Chlamydia pneumoniae","volume":"80","author":"Salin","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"14478","DOI":"10.1038\/ncomms14478","article-title":"Arylmethylamino steroids as antiparasitic agents","volume":"8","author":"Krieg","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1021\/ci100026x","article-title":"Drug-like bioactive structures and conformational coverage with the LigPrep\/ConfGen suite: Comparison to programs MOE and catalyst","volume":"50","author":"Chen","year":"2010","journal-title":"J. Chem. Inf. Model."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1007\/s10822-006-9087-6","article-title":"PHASE: A new engine for pharmacophore perception, 3D QSAR model development, and 3D database screening: 1. Methodology and preliminary results","volume":"20","author":"Dixon","year":"2006","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.drudis.2011.07.007","article-title":"A quality alert and call for improved curation of public chemistry databases","volume":"16","author":"Williams","year":"2011","journal-title":"Drug Discov. Today"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.3389\/fmicb.2018.03257","article-title":"Troglitazone Impedes the Oligomerization of Sodium Taurocholate Cotransporting Polypeptide and Entry of Hepatitis B Virus Into Hepatocytes","volume":"9","author":"Fukano","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1124\/jpet.106.102657","article-title":"Ritonavir, saquinavir, and efavirenz, but not nevirapine, inhibit bile acid transport in human and rat hepatocytes","volume":"318","author":"McRae","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1021\/mp300453k","article-title":"Structure-activity relationship for FDA approved drugs as inhibitors of the human sodium taurocholate cotransporting polypeptide (NTCP)","volume":"10","author":"Dong","year":"2013","journal-title":"Mol. Pharm."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Liu, Y., Ruan, H., Li, Y., Sun, G., Liu, X., He, W., Mao, F., He, M., Yan, L., and Zhong, G. (2020). Potent and Specific Inhibition of NTCP-Mediated HBV\/HDV Infection and Substrate Transporting by a Novel, Oral-Available Cyclosporine A Analogue. J. Med. Chem.","DOI":"10.1021\/acs.jmedchem.0c01484"},{"key":"ref_39","first-page":"549","article-title":"Screening and verifying potential NTCP inhibitors from herbal medicinal ingredients using the LLC-PK1 cell model stably expressing human NTCP","volume":"14","author":"Shen","year":"2016","journal-title":"Chin. J. Nat. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.ijpharm.2014.11.022","article-title":"A substrate pharmacophore for the human sodium taurocholate co-transporting polypeptide","volume":"478","author":"Dong","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Saso, W., Tsukuda, S., Ohashi, H., Fukano, K., Morishita, R., Matsunaga, S., Ohki, M., Ryo, A., Park, S.Y., and Suzuki, R. (2018). A new strategy to identify hepatitis B virus entry inhibitors by AlphaScreen technology targeting the envelope-receptor interaction. Biochem. Biophys. Res. Commun.","DOI":"10.1016\/j.bbrc.2018.04.187"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1152\/ajpgi.00352.2002","article-title":"Substrate specificities of rat oatp1 and ntcp: Implications for hepatic organic anion uptake","volume":"285","author":"Hata","year":"2003","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1124\/dmd.105.008748","article-title":"Inhibition of bile acid transport across Na+\/taurocholate cotransporting polypeptide (SLC10A1) and bile salt export pump (ABCB 11)-coexpressing LLC-PK1 cells by cholestasis-inducing drugs","volume":"34","author":"Mita","year":"2006","journal-title":"Drug Metab. Dispos."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.jhep.2013.11.022","article-title":"Cyclosporin A inhibits hepatitis B and hepatitis D virus entry by cyclophilin-independent interference with the NTCP receptor","volume":"60","author":"Nkongolo","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.jhep.2016.11.009","article-title":"Cyclosporin derivatives inhibit hepatitis B virus entry without interfering with NTCP transporter activity","volume":"66","author":"Shimura","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1002\/hep.26982","article-title":"Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP)","volume":"59","author":"Watashi","year":"2014","journal-title":"Hepatology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejps.2014.09.005","article-title":"Quantitative NTCP pharmacophore and lack of association between DILI and NTCP Inhibition","volume":"66","author":"Dong","year":"2015","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S1477-3627(02)02283-3","article-title":"GPCRs: An update on structural approaches to drug discovery","volume":"2","author":"Beeley","year":"2003","journal-title":"Targets"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.drudis.2006.05.012","article-title":"Virtual ligand screening: Strategies, perspectives and limitations","volume":"11","author":"Klebe","year":"2006","journal-title":"Drug Discov. Today"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.str.2004.02.031","article-title":"Heterogeneity and inaccuracy in protein structures solved by X-ray crystallography","volume":"12","author":"DePristo","year":"2004","journal-title":"Structure"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Srivastava, A., Nagai, T., Srivastava, A., Miyashita, O., and Tama, F. (2018). Role of Computational Methods in Going beyond X-ray Crystallography to Explore Protein Structure and Dynamics. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113401"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.4155\/fmc-2016-0093","article-title":"AutoQSAR: An automated machine learning tool for best-practice QSAR modeling","volume":"8","author":"Dixon","year":"2016","journal-title":"Future Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"158960","DOI":"10.1016\/j.bbalip.2021.158960","article-title":"Molecular regulation of the hepatic bile acid uptake transporter and HBV entry receptor NTCP","volume":"1866","author":"Appelman","year":"2021","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/8\/1489\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:36:44Z","timestamp":1760164604000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/8\/1489"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,29]]},"references-count":53,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["v13081489"],"URL":"https:\/\/doi.org\/10.3390\/v13081489","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,29]]}}}