{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:53:30Z","timestamp":1792788810794,"version":"4.5.0"},"reference-count":68,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Management and Science University","award":["SG-018-022020-SGS"],"award-info":[{"award-number":["SG-018-022020-SGS"]}],"id":[{"id":"https:\/\/ror.org\/027zr9y17","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Over the centuries, hyperlipidaemia has been recognised as a major risk factor contributing to cardiovascular disease (CVD). Current research increasingly explores natural compounds such as flavonoids for their potential lipid-lowering effects. This study evaluated pharmacological potential of flavonoids to identify strong inhibitors for target receptor, Proprotein Convertase Subtilisin\/Kexin Type (PCSK9). A total of 29 compounds, including one FDA-approved drugs were screened for drug-likeness and ADMET properties, followed by molecular docking and Molecular Dynamics (MD) simulations using PCSK9 receptor containing glucose and sodium (PDB ID: 5OCA). This complex was chosen due to their functional relevance to cholesterol metabolism. As a results, 24 compounds satisfied Lipinski\u2019s Rule of Five and exhibited favourable drug-likeness and toxicity profiles. Simvastatin (control) was discovered to bind into the pocket B binding site along with seven flavonoids; Diosmetin, Eupatorin, Isorhamnetin, Myricetin, Petunidin, Sinensetin, and Tilianin. These flavonoids displayed docking energies ranging from \u22128.0 to \u221210.2 kcal\/mol. Tilianin showed the strongest affinity (\u221210.2 kcal\/mol), while Simvastatin bound with \u22129.1 kcal\/mol. MD simulations confirmed that the PCSK9-ligand complexes remained structurally stable throughout a 100 ns trajectory. MM\/PBSA analysis further supported the binding interactions, revealing free energies values ranging from \u221217 to \u221230.41 kcal\/mol. Among the flavonoids evaluated, Tilianin, Myricetin, and Sinensetin demonstrate the most favourable interaction profiles. These finding suggest that the selected flavonoids have strong potential as promising anti-hyperlipidaemic candidates targeting PCSK9.<\/jats:p>","DOI":"10.1371\/journal.pone.0346073","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:42:21Z","timestamp":1791567741000},"page":"e0346073","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of flavonoids from natural products against hyperlipidaemia through computational approaches"],"prefix":"10.1371","volume":"21","author":[{"given":"Nurnazira Hanis","family":"Mustaffar Kamal","sequence":"first","affiliation":[{"name":"Postgraduate Centre Management and Science University, University Drive","place":["Shah Alam, Selangor, Malaysia"],"department":["School of Graduate Studies"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5368-0810","authenticated-orcid":true,"given":"Nurul Azira","family":"Ismail","sequence":"additional","affiliation":[{"name":"Postgraduate Centre Management and Science University, University Drive","place":["Shah Alam, Selangor, Malaysia"],"department":["School of Graduate Studies"]},{"name":"Management and Science University, University Drive","place":["Shah Alam, Selangor, Malaysia"],"department":["Faculty of Health and Life Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernie Zuraida","family":"Ali","sequence":"additional","affiliation":[{"name":"Institute for Medical Research, National Institutes of Health Malaysia","place":["Shah Alam, Selangor, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"issue":"8","key":"pone.0346073.ref001","article-title":"Heart disease and stroke statistics\u20142022 update: A report from the american heart association","volume":"145","author":"CW Tsao","year":"2022","journal-title":"Circulation"},{"issue":"14","key":"pone.0346073.ref002","doi-asserted-by":"crossref","first-page":"8272","DOI":"10.3390\/ijerph19148272","article-title":"Serum cholesterol levels and risk of cardiovascular death: A systematic review and a dose-response meta-analysis of prospective cohort studies","volume":"19","author":"E Jung","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"pone.0346073.ref003","volume-title":"National health & morbidity survey 2015 (NHMS 2015)","author":"Institute for Public Health","year":"2015"},{"key":"pone.0346073.ref004","author":"KR Feingold","year":"2024"},{"issue":"7","key":"pone.0346073.ref005","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2020.e04545","article-title":"Interaction of different lipoprotein types with cholesterol at the air\/water interface","volume":"6","author":"R Ninomiya","year":"2020","journal-title":"Heliyon"},{"key":"pone.0346073.ref006","author":"KR Feingold","year":"2024"},{"issue":"2","key":"pone.0346073.ref007","doi-asserted-by":"crossref","first-page":"240372","DOI":"10.1098\/rsob.240372","article-title":"High-density lipoprotein cholesterol: How studying the \u201cgood cholesterol\u201d could improve cardiovascular health","volume":"15","author":"L Diaz","year":"2025","journal-title":"Open Biol"},{"issue":"2","key":"pone.0346073.ref008","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/ng1161","article-title":"Mutations in PCSK9 cause autosomal dominant hypercholesterolemia","volume":"34","author":"M Abifadel","year":"2003","journal-title":"Nat Genet"},{"issue":"3","key":"pone.0346073.ref009","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1086\/500615","article-title":"A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol","volume":"78","author":"IK Kotowski","year":"2006","journal-title":"Am J Hum Genet"},{"issue":"11","key":"pone.0346073.ref010","doi-asserted-by":"crossref","first-page":"5880","DOI":"10.3390\/ijms22115880","article-title":"PCSK9 biology and its role in atherothrombosis","volume":"22","author":"C Barale","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"6","key":"pone.0346073.ref011","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1161\/CIRCRESAHA.114.301621","article-title":"PCSK9: A key modulator of cardiovascular health","volume":"114","author":"NG Seidah","year":"2014","journal-title":"Circ Res"},{"issue":"10","key":"pone.0346073.ref012","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1038\/s41401-024-01305-9","article-title":"A novel small-molecule PCSK9 inhibitor E28362 ameliorates hyperlipidemia and atherosclerosis","volume":"45","author":"W-Z Wang","year":"2024","journal-title":"Acta Pharmacol Sin"},{"issue":"2","key":"pone.0346073.ref013","first-page":"190","article-title":"PCSK9 promotes cardiovascular diseases: recent evidence about its association with platelet activation-induced myocardial infarction","volume":"12","author":"MU Puteri","year":"2022","journal-title":"Life (Basel)"},{"issue":"3","key":"pone.0346073.ref014","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1097\/MOL.0000000000000601","article-title":"Proprotein convertase subtilisin\/kexin type 9 and lipid metabolism","volume":"30","author":"S Spolitu","year":"2019","journal-title":"Curr Opin Lipidol"},{"issue":"10","key":"pone.0346073.ref015","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1001\/jamacardio.2017.2762","article-title":"Cost-effectiveness of evolocumab therapy for reducing cardiovascular events in patients with atherosclerotic cardiovascular disease","volume":"2","author":"GC Fonarow","year":"2017","journal-title":"JAMA Cardiol"},{"issue":"1","key":"pone.0346073.ref016","first-page":"203","article-title":"The effect of PCSK9 immunization on the hepatic level of microRNAs associated with the PCSK9\/LDLR pathway","volume":"19","author":"S Ataei","year":"2023","journal-title":"Arch Med Sci"},{"issue":"39","key":"pone.0346073.ref017","article-title":"Polyphenol-based functional materials: Structural insights, composite strategies, and biomedical applications","volume":"12","author":"S Xue","year":"2025","journal-title":"Adv Sci (Weinh)"},{"issue":"4","key":"pone.0346073.ref018","doi-asserted-by":"crossref","first-page":"360","DOI":"10.4103\/tcmj.tcmj_46_24","article-title":"Natural phytochemicals as small-molecule proprotein convertase subtilisin\/kexin type 9 inhibitors","volume":"36","author":"J-W Liou","year":"2024","journal-title":"Tzu Chi Med J"},{"key":"pone.0346073.ref019","doi-asserted-by":"crossref","first-page":"100701","DOI":"10.1016\/j.prmcm.2025.100701","article-title":"Therapeutic potential of flavonoid-enriched Chinese medicinal herbs in atherosclerosis, hypertension, myocardial infarction, and heart failure","volume":"17","author":"D Jaisankar","year":"2025","journal-title":"Pharmacol Res Modern Chinese Med"},{"issue":"2","key":"pone.0346073.ref020","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1002\/fsn3.765","article-title":"Effects of Talinum triangulare leaf flavonoid extract on streptozotocin-induced hyperglycemia and associated complications in rats","volume":"7","author":"OM Oluba","year":"2018","journal-title":"Food Sci Nutr"},{"issue":"37","key":"pone.0346073.ref021","doi-asserted-by":"crossref","first-page":"9777","DOI":"10.1021\/acs.jafc.8b03568","article-title":"Effects of natural flavonoid isoorientin on growth performance and gut microbiota of mice","volume":"66","author":"L Yuan","year":"2018","journal-title":"J Agric Food Chem"},{"issue":"2","key":"pone.0346073.ref022","doi-asserted-by":"crossref","first-page":"346","DOI":"10.3390\/molecules30020346","article-title":"Mechanistic insights into the anticancer potential of methoxyflavones analogs: A review","volume":"30","author":"M Aidiel","year":"2025","journal-title":"Molecules"},{"key":"pone.0346073.ref023","doi-asserted-by":"crossref","first-page":"139269","DOI":"10.1016\/j.molstruc.2024.139269","article-title":"Anti-inflammatory activity evaluation and molecular docking analysis of four new compounds isolated from M. oleifera seeds","volume":"1318","author":"Z Wang","year":"2024","journal-title":"J Mol Struc"},{"issue":"1","key":"pone.0346073.ref024","doi-asserted-by":"crossref","DOI":"10.1186\/s43088-021-00117-8","article-title":"Investigating the binding affinity, molecular dynamics, and ADMET properties of 2,3-dihydrobenzofuran derivatives as an inhibitor of fungi, bacteria, and virus protein","volume":"10","author":"A Nath","year":"2021","journal-title":"Beni-Suef Univ J Basic Appl Sci"},{"key":"pone.0346073.ref025","doi-asserted-by":"crossref","first-page":"131915","DOI":"10.1016\/j.molstruc.2021.131915","article-title":"Synthesis, molecular docking, molecular dynamic, quantum calculation, and antibacterial activity of new Schiff base-metal complexes","volume":"1250","author":"HE Hashem","year":"2022","journal-title":"Journal of Molecular Structure"},{"issue":"2","key":"pone.0346073.ref026","doi-asserted-by":"crossref","first-page":"5206","DOI":"10.4067\/S0717-97072021000205206","article-title":"Computational investigation of methyl \u03b1-d-glucopyranoside derivatives as inhibitor against bacteria, fungi and COVID-19 (SARS-2)","volume":"66","author":"SMA Kawsar","year":"2021","journal-title":"J Chil Chem Soc"},{"issue":"12","key":"pone.0346073.ref027","doi-asserted-by":"crossref","first-page":"3694","DOI":"10.3390\/molecules27123694","article-title":"Investigation of the new inhibitors by sulfadiazine and modified derivatives of \u03b1-D-glucopyranoside for white spot syndrome virus disease of shrimp by in silico: Quantum calculations, molecular docking, admet and molecular dynamics study","volume":"27","author":"A Kumer","year":"2022","journal-title":"Molecules"},{"issue":"2","key":"pone.0346073.ref028","doi-asserted-by":"crossref","first-page":"504","DOI":"10.3390\/molecules23020504","article-title":"Discovery of flavonoids from scutellaria baicalensis with inhibitory activity against PCSK 9 expression: Isolation, synthesis and their biological evaluation","volume":"23","author":"P Nhoek","year":"2018","journal-title":"Molecules"},{"key":"pone.0346073.ref029","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1758-2946-3-33","article-title":"Open Babel: An open chemical toolbox","volume":"3","author":"NM O\u2019Boyle","year":"2011","journal-title":"J Cheminform"},{"key":"pone.0346073.ref030","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":"A Daina","year":"2017","journal-title":"Sci Rep"},{"issue":"5","key":"pone.0346073.ref031","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1093\/nar\/gky092","article-title":"UniProt: The universal protein knowledgebase","volume":"46","author":"UniProt Consortium T","year":"2018","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"pone.0346073.ref032","doi-asserted-by":"crossref","DOI":"10.1002\/wcms.1298","article-title":"Using PyMOL as a platform for computational drug design","volume":"7","author":"S Yuan","year":"2017","journal-title":"WIREs Comput Mol Sci"},{"issue":"1","key":"pone.0346073.ref033","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/s41467-017-00568-7","article-title":"Heparan sulfate proteoglycans present PCSK9 to the LDL receptor","volume":"8","author":"C Gustafsen","year":"2017","journal-title":"Nat Commun"},{"key":"pone.0346073.ref034","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gku340","article-title":"SWISS-MODEL: Modelling protein tertiary and quaternary structure using evolutionary information","volume":"42","author":"M Biasini","year":"2014","journal-title":"Nucleic Acids Res"},{"issue":"13","key":"pone.0346073.ref035","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1093\/nar\/gkg520","article-title":"SWISS-MODEL: An automated protein homology-modeling server","volume":"31","author":"T Schwede","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"pone.0346073.ref036","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/978-1-61779-588-6_10","article-title":"Methods of protein structure comparison","volume":"857","author":"I Kufareva","year":"2012","journal-title":"Methods Mol Biol"},{"issue":"2","key":"pone.0346073.ref037","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":"O Trott","year":"2010","journal-title":"J Comput Chem"},{"key":"pone.0346073.ref038","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","author":"MJ Abraham","year":"2015","journal-title":"SoftwareX"},{"issue":"8","key":"pone.0346073.ref039","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1002\/prot.22711","article-title":"Improved side-chain torsion potentials for the Amber ff99SB protein force field","volume":"78","author":"K Lindorff-Larsen","year":"2010","journal-title":"Proteins"},{"issue":"5","key":"pone.0346073.ref040","doi-asserted-by":"crossref","first-page":"389","DOI":"10.3390\/biology10050389","article-title":"Molecular docking and dynamics simulation study of hyrtios erectus isolated scalarane sesterterpenes as potential SARS-CoV-2 dual target inhibitors","volume":"10","author":"SS Elhady","year":"2021","journal-title":"Biology"},{"issue":"4","key":"pone.0346073.ref041","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s12539-016-0157-8","article-title":"Molecular docking and molecular dynamics simulation studies to predict flavonoid binding on the surface of DENV2 E protein","volume":"9","author":"NA Ismail","year":"2017","journal-title":"Interdiscip Sci"},{"issue":"1","key":"pone.0346073.ref042","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s43141-020-00041-x","article-title":"In silico structural modeling and analysis of physicochemical properties of curcumin synthase (CURS1, CURS2, and CURS3) proteins of Curcuma longa","volume":"18","author":"R Santhoshkumar","year":"2020","journal-title":"J Genet Eng Biotechnol"},{"issue":"1","key":"pone.0346073.ref043","first-page":"2347","article-title":"Homology Modelling of Pseudomonas stutzeri ZS04 Lipase","volume":"9","author":"F Fatmawati","year":"2023","journal-title":"Quest Journals J Res Pharma Sci"},{"issue":"3","key":"pone.0346073.ref044","doi-asserted-by":"crossref","first-page":"347","DOI":"10.20473\/jfiki.v10i32023.347-359","article-title":"Analysis of molecular docking and dynamics simulation of mahogany (Swietenia macrophylla King) compounds against the PLpro enzyme SARS-COV-2","volume":"10","author":"A Lalu Sanik Wahyu Fadil","year":"2023","journal-title":"JFIKI"},{"key":"pone.0346073.ref045","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1742-4682-10-22","article-title":"Homology modeling and virtual screening approaches to identify potent inhibitors of VEB-1 \u03b2-lactamase","volume":"10","author":"A Messaoudi","year":"2013","journal-title":"Theor Biol Med Model"},{"issue":"12","key":"pone.0346073.ref046","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.1080\/07391102.2017.1377635","article-title":"In silico and empirical approaches toward understanding the structural adaptation of the alkaline-stable lipase KV1 from Acinetobacter haemolyticus","volume":"36","author":"K Batumalaie","year":"2018","journal-title":"J Biomol Struct Dyn"},{"key":"pone.0346073.ref047","article-title":"Regulation of PCSK9 expression and function: mechanisms and therapeutic implications","volume":"8","author":"X Xia","year":"2021","journal-title":"Frontiers in Cardiovascular Medicine"},{"issue":"27","key":"pone.0346073.ref048","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.1093\/eurheartj\/ehx710","article-title":"\u201cHighest risk-highest benefit\u201d strategy: A pragmatic, cost-effective approach to targeting use of PCSK9 inhibitor therapies","volume":"39","author":"L Annemans","year":"2018","journal-title":"Eur Heart J"},{"issue":"2","key":"pone.0346073.ref049","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1002\/cpt.1193","article-title":"Adverse events associated with PCSK9 inhibitors: A real-world experience","volume":"105","author":"MT G\u00fcrg\u00f6ze","year":"2019","journal-title":"Clin Pharmacol Ther"},{"issue":"1","key":"pone.0346073.ref050","first-page":"75","article-title":"Profiling GC-MS ethanol extract of putri malu leaves (Mimosa pudica L.) and it\u2019s potential as anti-cholesterol in vitro","volume":"8","author":"D Adhityasmara","year":"2022","journal-title":"Jurnal Kimia dan Pendidikan Kimia"},{"issue":"10","key":"pone.0346073.ref051","doi-asserted-by":"crossref","first-page":"4644","DOI":"10.1039\/D0FO03366A","article-title":"Drug-guided screening for pancreatic lipase inhibitors in functional foods","volume":"12","author":"L Zhang","year":"2021","journal-title":"Food Funct"},{"issue":"18","key":"pone.0346073.ref052","doi-asserted-by":"crossref","first-page":"4320","DOI":"10.3390\/molecules25184320","article-title":"The effects of flavonoids in cardiovascular diseases","volume":"25","author":"L Cium\u0103rnean","year":"2020","journal-title":"Molecules"},{"key":"pone.0346073.ref053","doi-asserted-by":"crossref","first-page":"7092151","DOI":"10.1155\/2019\/7092151","article-title":"Vascular inflammation and oxidative stress: Major triggers for cardiovascular disease","volume":"2019","author":"S Steven","year":"2019","journal-title":"Oxid Med Cell Longev"},{"issue":"20","key":"pone.0346073.ref054","doi-asserted-by":"crossref","first-page":"10096","DOI":"10.3390\/ijms262010096","article-title":"Endothelial dysfunction as the common pathway linking obesity, hypertension and atherosclerosis","volume":"26","author":"E M\u0142ynarska","year":"2025","journal-title":"Int J Mol Sci"},{"key":"pone.0346073.ref055","first-page":"105364","article-title":"Polymethoxyflavones transcends expectation, a prominent flavonoid subclass from Kaempferia parviflora: A critical review","author":"M Aidiel","year":"2023","journal-title":"Arab J Chem"},{"issue":"3","key":"pone.0346073.ref056","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1093\/abbs\/gmy002","article-title":"Kaempferol protects ethanol-induced gastric ulcers in mice via pro-inflammatory cytokines and NO","volume":"50","author":"Q Li","year":"2018","journal-title":"Acta Biochim Biophys Sin (Shanghai)"},{"issue":"2","key":"pone.0346073.ref057","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s11357-009-9124-1","article-title":"Kaempferol modulates pro-inflammatory NF-kappaB activation by suppressing advanced glycation endproducts-induced NADPH oxidase","volume":"32","author":"JM Kim","year":"2010","journal-title":"Age (Dordr)"},{"key":"pone.0346073.ref058","doi-asserted-by":"crossref","first-page":"100981","DOI":"10.1016\/j.focha.2025.100981","article-title":"Systematic review on effectiveness of flavonoids against hypercholesterolemia: Insights from in-silico, in-vitro, and in-vivo studies","volume":"7","author":"N Hanis","year":"2025","journal-title":"Food Chemistry Advances"},{"issue":"1","key":"pone.0346073.ref059","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.atherosclerosis.2008.06.010","article-title":"Molecular basis of PCSK9 function","volume":"203","author":"G Lambert","year":"2009","journal-title":"Atherosclerosis"},{"key":"pone.0346073.ref060","article-title":"PCSK9: A convertase that coordinates LDL catabolism","author":"JD Horton","year":"2009","journal-title":"J Lipid Res"},{"issue":"10","key":"pone.0346073.ref061","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1194\/jlr.M018093","article-title":"Role of the C-terminal domain of PCSK9 in degradation of the LDL receptors","volume":"52","author":"\u00d8L Holla","year":"2011","journal-title":"J Lipid Res"},{"key":"pone.0346073.ref062","article-title":"Flavonoids from the leaves of Monanthotaxis filipes modulate PCSK9 and LDLR","author":"JG Mayeka","year":"2025","journal-title":"Scientific African"},{"issue":"45","key":"pone.0346073.ref063","doi-asserted-by":"crossref","first-page":"24534","DOI":"10.1039\/D5CP03269E","article-title":"Allosteric inhibition of the PCSK9-LDLR interaction: structural insights for small molecule design","volume":"27","author":"YS Baek","year":"2025","journal-title":"Phys Chem Chem Phys"},{"issue":"2","key":"pone.0346073.ref064","doi-asserted-by":"crossref","first-page":"286","DOI":"10.3390\/biomedicines12020286","article-title":"Targeting allosteric site of PCSK9 enzyme for the identification of small molecule inhibitors: An in silico drug repurposing study","volume":"12","author":"NB Charbe","year":"2024","journal-title":"Biomedicines"},{"issue":"8","key":"pone.0346073.ref065","article-title":"Eupatorin from Orthosiphon aristatus: A review of the botanical origin, pharmacological effects and isolation methods","volume":"19","author":"AA Arham","year":"2023","journal-title":"Current Bioactive Compounds"},{"key":"pone.0346073.ref066","doi-asserted-by":"crossref","first-page":"178330","DOI":"10.1016\/j.ejphar.2025.178330","article-title":"Eupatorin: A comprehensive review of its pharmacological activities and underlying molecular mechanisms","volume":"1008","author":"Y Hussain","year":"2025","journal-title":"Eur J Pharmacol"},{"issue":"12","key":"pone.0346073.ref067","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.3390\/ph17121597","article-title":"Carotenoid interactions with PCSK9: Exploring novel cholesterol-lowering strategies","volume":"17","author":"A Medoro","year":"2024","journal-title":"Pharmaceuticals (Basel)"},{"issue":"8","key":"pone.0346073.ref068","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0255523","article-title":"Finding inhibitors for PCSK9 using computational methods","volume":"16","author":"R Zainab","year":"2021","journal-title":"PLoS One"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0346073","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:42:32Z","timestamp":1791567752000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0346073"}},"subtitle":[],"editor":[{"given":"Jorddy Neves","family":"Cruz","sequence":"first","affiliation":[{"name":"Universidade Federal do Para","place":["BRAZIL"]}],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,10,9]]},"references-count":68,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,10,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0346073","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,9]]}}}