{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:51:50Z","timestamp":1791481910144,"version":"4.3.4"},"reference-count":143,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Saud University in Riyadh, Saudi Arabia.","award":["ORF-2025-740"],"award-info":[{"award-number":["ORF-2025-740"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>SARS-CoV-2 was identified at the end of 2019 as the key cause of COVID-19, a global pandemic. As remedies, different vaccines as well as synthetic drugs have been recommended. However, the availability of natural drugs against SARS-CoV-2 infection is limited, although natural drugs are considered as less toxic than synthetic drugs, and vaccine efficacy is gradually weakened due to unstable RNA sequence patterns of SARS-CoV-2. Black-cumin is a well-known medicinal plant, but it was not rigorously investigated against SARS-CoV-2 infections. This study attempted to investigate this issue, rigorously. In order to explore effective bioactive phytocompounds from black-cumin (BC) through bioinformatics analysis, we selected top-ranked 11 drug target proteins\/receptors of which five receptors were SARS-CoV-2 proteins\/proteases (S, N, RdRp, 3CLpro, PLpro) and the other six receptors were host proteins (ACE2, MAPK8, TMPRSS2, IL6, TNF, and NFKBIA) associated with the infection by the systematic literature review. We computed binding affinity scores (BAS) for each phytochemical of BC with each of those 11 receptors. Top-ranked five phytocompounds (Silibinin, Taraxerol, Beta amyrin, Cycloartenol, and Alpha-sitosterol) were selected based on their highest average BAS across our proposed receptor, these phytocompounds also showed better binding capabilities against the other independent receptors. Then we selected top-ranked three complexes (ACE2 vs. silibinin, Spike vs. beta amyrin, and MAPK8 vs. Taraxerol) to investigate their binding stability using dynamic simulation (i.e., RMSD, RMSF, DCCM, PCA, and FEL) and MM-GBSA studies and found their stable performance. The ADMET, Bioactivity, and DFT analysis results supported the drug-likeness properties of the proposed phytocompounds. Therefore, the findings of this article might be useful resources for taking an alternative treatment plan against SARS-CoV-2 infections.<\/jats:p>","DOI":"10.1371\/journal.pone.0337970","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T17:42:10Z","timestamp":1773250930000},"page":"e0337970","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exploring potential phytocompounds from black cumin as drug molecules against SARS-CoV-2 infections through bioinformatics analysis"],"prefix":"10.1371","volume":"21","author":[{"given":"Md. Ahad","family":"Ali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humaira","family":"Sheikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Selim","family":"Reza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tripti Rani","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tasfia","family":"Noor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeraj","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mashooq Ahmad","family":"Bhat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3883-3396","authenticated-orcid":true,"given":"Md. Nurul Haque","family":"Mollah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"issue":"6","key":"pone.0337970.ref001","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1001\/jama.2020.27124","article-title":"Genetic Variants of SARS-CoV-2-What Do They Mean?","volume":"325","author":"AS Lauring","year":"2021","journal-title":"JAMA"},{"issue":"2","key":"pone.0337970.ref002","doi-asserted-by":"crossref","DOI":"10.1128\/Spectrum.00789-21","article-title":"The Emergence of Sars-CoV-2 Variant Lambda (C.37) in South America","volume":"9","author":"PE Romero","year":"2021","journal-title":"Microbiol Spectr"},{"issue":"7887","key":"pone.0337970.ref003","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/d41586-021-03552-w","article-title":"Heavily mutated Omicron variant puts scientists on alert","volume":"600","author":"E 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Accessed 2023 October 1."},{"key":"pone.0337970.ref074","volume-title":"The PyMOL Molecular Graphics System","author":"WL DeLano","year":"2002"},{"key":"pone.0337970.ref075","volume-title":"Biovia Discovery Studio Modeling Environment","year":"2020"},{"issue":"15","key":"pone.0337970.ref076","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1002\/elps.1150181505","article-title":"SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling","volume":"18","author":"N Guex","year":"1997","journal-title":"Electrophoresis"},{"issue":"1","key":"pone.0337970.ref077","doi-asserted-by":"crossref","first-page":"4329","DOI":"10.1038\/s41598-018-22631-z","article-title":"IMPPAT: A curated database of Indian Medicinal Plants, Phytochemistry And Therapeutics","volume":"8","author":"K Mohanraj","year":"2018","journal-title":"Sci Rep"},{"key":"pone.0337970.ref078","article-title":"PubChem Substance and Compound databases","volume":"44","author":"S Kim","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"pone.0337970.ref079","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.0337970.ref080","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":"S Dallakyan","year":"2015","journal-title":"Methods Mol Biol"},{"issue":"4","key":"pone.0337970.ref081","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ddtec.2004.11.007","article-title":"Lead- and drug-like compounds: the rule-of-five revolution","volume":"1","author":"CA Lipinski","year":"2004","journal-title":"Drug Discov Today Technol"},{"issue":"1","key":"pone.0337970.ref082","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S1056-8719(00)00107-6","article-title":"Drug-like properties and the causes of poor solubility and poor permeability","volume":"44","author":"CA Lipinski","year":"2000","journal-title":"J Pharmacol Toxicol Methods"},{"issue":"12","key":"pone.0337970.ref083","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1021\/jm020017n","article-title":"Molecular properties that influence the oral bioavailability of drug candidates","volume":"45","author":"DF Veber","year":"2002","journal-title":"J Med Chem"},{"key":"pone.0337970.ref084","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkab255","article-title":"ADMETlab 2.0: an integrated online platform for accurate and comprehensive predictions of ADMET properties","volume":"49","author":"G Xiong","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"pone.0337970.ref085","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":"2","key":"pone.0337970.ref086","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.0337970.ref087","doi-asserted-by":"crossref","DOI":"10.1016\/j.sciaf.2025.e02634","article-title":"Computational screening campaign reveal natural candidates as potential ASK1 inhibitors: Pharmacophore modeling, molecular docking, MMGBSA calculations, ADMET prediction, and molecular dynamics simulation studies","volume":"28","author":"R Yousif","year":"2025","journal-title":"Scientific African"},{"issue":"24","key":"pone.0337970.ref088","doi-asserted-by":"crossref","first-page":"7796","DOI":"10.1021\/jm050306m","article-title":"Evaluating the molecular mechanics poisson-boltzmann surface area free energy method using a congeneric series of ligands to p38 MAP kinase","volume":"48","author":"DA Pearlman","year":"2005","journal-title":"J Med Chem"},{"issue":"9","key":"pone.0337970.ref089","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","article-title":"pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures","volume":"58","author":"DEV Pires","year":"2015","journal-title":"J Med Chem"},{"key":"pone.0337970.ref090","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkae303","article-title":"ProTox 3.0: a webserver for the prediction of toxicity of chemicals","volume":"52","author":"P Banerjee","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"pone.0337970.ref091","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s002149900065","article-title":"Perspective on \u201cDensity functional thermochemistry. III. The role of exact exchange\u201d","volume":"103","author":"K Raghavachari","year":"2000","journal-title":"Theoretical Chemistry Accounts: Theory, Computation, and Modeling (Theoretica Chimica Acta)"},{"key":"pone.0337970.ref092","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S0009-2614(97)00207-8","article-title":"On the parameterization of the local correlation functional. What is Becke-3-LYP?","volume":"268","author":"RH Hertwig","year":"1997","journal-title":"Chemical Physics Letters"},{"key":"pone.0337970.ref093","volume-title":"Gaussian 09, Revision B.01","author":"MJ Frisch","year":"2009"},{"issue":"8","key":"pone.0337970.ref094","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2020.e04642","article-title":"Virtual screening, molecular docking studies and DFT calculations of FDA approved compounds similar to the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz","volume":"6","author":"MA Jordaan","year":"2020","journal-title":"Heliyon"},{"issue":"1","key":"pone.0337970.ref095","doi-asserted-by":"crossref","first-page":"52","DOI":"10.33263\/BRIAC131.052","article-title":"Uridine-Derived 4-Aminophenyl 1-Thioglucosides: DFT Optimized FMO, ADME, and Antiviral Activities Study","volume":"13","year":"2022","journal-title":"Biointerface Res Appl Chem"},{"key":"pone.0337970.ref096","volume-title":"Gauss View","author":"R Dennington","year":"2009"},{"key":"pone.0337970.ref097","unstructured":"U.S. Food & Drug Administration Coronavirus (COVID-19) | Drugs Available. https:\/\/www.fda.gov\/drugs\/emergency-preparedness-drugs\/coronavirus-covid-19-drugs"},{"issue":"5","key":"pone.0337970.ref098","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1016\/j.bmcl.2012.12.047","article-title":"Development of amino-pyrimidine inhibitors of c-Jun N-terminal kinase (JNK): kinase profiling guided optimization of a 1,2,3-benzotriazole lead","volume":"23","author":"WS Palmer","year":"2013","journal-title":"Bioorg Med Chem Lett"},{"issue":"5742","key":"pone.0337970.ref099","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1126\/science.1116480","article-title":"Structure of SARS coronavirus spike receptor-binding domain complexed with receptor","volume":"309","author":"F Li","year":"2005","journal-title":"Science"},{"issue":"6582","key":"pone.0337970.ref100","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1126\/science.abn7760","article-title":"SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein-ACE2 complex","volume":"375","author":"D Mannar","year":"2022","journal-title":"Science"},{"issue":"44","key":"pone.0337970.ref101","doi-asserted-by":"crossref","first-page":"36938","DOI":"10.1039\/D5RA05535K","article-title":"Multi-omics pan-cancer profiling of CDK2 and in silico identification of plant-derived inhibitors using machine learning approaches","volume":"15","author":"MA Ali","year":"2025","journal-title":"RSC Adv"},{"issue":"4","key":"pone.0337970.ref102","article-title":"Structure-based 3D-Pharmacophore modeling to discover novel interleukin 6 inhibitors: An in silico screening, molecular dynamics simulations and binding free energy calculations","volume":"17","author":"Q-H Tran","year":"2022","journal-title":"PLoS One"},{"key":"pone.0337970.ref103","doi-asserted-by":"crossref","unstructured":"Kibria K, Ali A, Yaseen M, Khan IA, Bhat MA, Islam A, et al. Discovery of bacterial key genes from 16S rRNA-seq profiles that are associated with the complications of SARS-CoV-2 infections and provide therapeutic indications. 2024;2019.","DOI":"10.3390\/ph17040432"},{"key":"pone.0337970.ref104","doi-asserted-by":"crossref","first-page":"128933","DOI":"10.1016\/j.foodchem.2020.128933","article-title":"An in-silico evaluation of different bioactive molecules of tea for their inhibition potency against non structural protein-15 of SARS-CoV-2","volume":"346","author":"J Sharma","year":"2021","journal-title":"Food Chem"},{"issue":"22","key":"pone.0337970.ref105","doi-asserted-by":"crossref","first-page":"12194","DOI":"10.1080\/07391102.2021.1969280","article-title":"Synthesis, spectroscopic characterization, antimicrobial activity, molecular docking and DFT studies of proton transfer (H-bonded) complex of 8-aminoquinoline (donor) with chloranilic acid (acceptor)","volume":"40","author":"IM Khan","year":"2022","journal-title":"J Biomol Struct Dyn"},{"issue":"6","key":"pone.0337970.ref106","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1080\/07391102.2020.1839563","article-title":"Targeting SARS-CoV-2 nucleocapsid oligomerization: Insights from molecular docking and molecular dynamics simulations","volume":"40","author":"S Ahamad","year":"2022","journal-title":"J Biomol Struct Dyn"},{"key":"pone.0337970.ref107","doi-asserted-by":"crossref","first-page":"1222913","DOI":"10.3389\/fcimb.2023.1222913","article-title":"Anti-parasitic drug discovery against Babesia microti by natural compounds: an extensive computational drug design approach","volume":"13","author":"S Akash","year":"2023","journal-title":"Front Cell Infect Microbiol"},{"issue":"5","key":"pone.0337970.ref108","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1517\/17460441.2015.1032936","article-title":"The MM\/PBSA and MM\/GBSA methods to estimate ligand-binding affinities","volume":"10","author":"S Genheden","year":"2015","journal-title":"Expert Opin Drug Discov"},{"issue":"4","key":"pone.0337970.ref109","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1002\/minf.201000118","article-title":"In Silico Prediction of Caco-2 Cell Permeability by a Classification QSAR Approach","volume":"30","author":"H Pham The","year":"2011","journal-title":"Mol Inform"},{"issue":"1","key":"pone.0337970.ref110","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13321-018-0283-x","article-title":"ADMETlab: a platform for systematic ADMET evaluation based on a comprehensively collected ADMET database","volume":"10","author":"J Dong","year":"2018","journal-title":"J Cheminform"},{"key":"pone.0337970.ref111","author":"D Blumenthal","year":"2006","journal-title":"Goodman and Gilman\u2019s Pharmacological Basis of Therapeutics Digital Edition"},{"issue":"11","key":"pone.0337970.ref112","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1002\/cmdc.201600182","article-title":"A BOILED-Egg To Predict Gastrointestinal Absorption and Brain Penetration of Small Molecules","volume":"11","author":"A Daina","year":"2016","journal-title":"ChemMedChem"},{"issue":"3","key":"pone.0337970.ref113","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1021\/ci034243x","article-title":"ESOL: estimating aqueous solubility directly from molecular structure","volume":"44","author":"JS Delaney","year":"2004","journal-title":"J Chem Inf Comput Sci"},{"issue":"4","key":"pone.0337970.ref114","doi-asserted-by":"crossref","first-page":"911","DOI":"10.3390\/molecules23040911","article-title":"Evaluating Molecular Properties Involved in Transport of Small Molecules in Stratum Corneum: A Quantitative Structure-Activity Relationship for Skin Permeability","volume":"23","author":"C-P Chen","year":"2018","journal-title":"Molecules"},{"issue":"17","key":"pone.0337970.ref115","doi-asserted-by":"crossref","first-page":"174101","DOI":"10.1063\/1.3491272","article-title":"On Koopmans\u2019 theorem in density functional theory","volume":"133","author":"T Tsuneda","year":"2010","journal-title":"J Chem Phys"},{"issue":"11","key":"pone.0337970.ref116","doi-asserted-by":"crossref","first-page":"2524","DOI":"10.3390\/molecules29112524","article-title":"Exploring the Therapeutic Potential of Petiveria alliacea L. Phytochemicals: A Computational Study on Inhibiting SARS-CoV-2\u2019s Main Protease (Mpro)","volume":"29","author":"MA Ali","year":"2024","journal-title":"Molecules"},{"issue":"14","key":"pone.0337970.ref117","doi-asserted-by":"crossref","first-page":"9878","DOI":"10.1039\/D4RA01070A","article-title":"ADME profiling, molecular docking, DFT, and MEP analysis reveal cissamaline, cissamanine, and cissamdine from Cissampelos capensis L.f. as potential anti-Alzheimer\u2019s agents","volume":"14","author":"MB Alhawarri","year":"2024","journal-title":"RSC Adv"},{"key":"pone.0337970.ref118","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1107\/S2056989019017353","article-title":"Crystal structure, DFT and MEP study of (E)-2-{[(3-chloro-phen-yl)imino]-meth-yl}-6-methyl-phenol","volume":"76","author":"H Sara\u00e7o\u011flu","year":"2020","journal-title":"Acta Crystallogr E Crystallogr Commun"},{"key":"pone.0337970.ref119","doi-asserted-by":"crossref","first-page":"128715","DOI":"10.1016\/j.molstruc.2020.128715","article-title":"DFT studies on vibrational and electronic spectra, HOMO-LUMO, MEP, HOMA, NBO and molecular docking analysis of benzyl-3-N-(2,4,5-trimethoxyphenylmethylene)hydrazinecarbodithioate","volume":"1220","author":"MA Mumit","year":"2020","journal-title":"J Mol Struct"},{"key":"pone.0337970.ref120","doi-asserted-by":"crossref","first-page":"625386","DOI":"10.3389\/fphar.2021.625386","article-title":"Nigella Plants - Traditional Uses, Bioactive Phytoconstituents, Preclinical and Clinical Studies","volume":"12","author":"B Salehi","year":"2021","journal-title":"Front Pharmacol"},{"issue":"10","key":"pone.0337970.ref121","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.3390\/nu13103369","article-title":"The Role of Bioactive Compounds of Nigella sativa in Rheumatoid Arthritis Therapy-Current Reports","volume":"13","author":"M Zieli\u0144ska","year":"2021","journal-title":"Nutrients"},{"issue":"1","key":"pone.0337970.ref122","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2174\/1389201019666180427110007","article-title":"Nigella sativa L. and Its Bioactive Constituents as Hepatoprotectant: A Review","volume":"19","author":"H Tabassum","year":"2018","journal-title":"Curr Pharm Biotechnol"},{"issue":"5","key":"pone.0337970.ref123","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S2221-1691(13)60075-1","article-title":"A review on therapeutic potential of Nigella sativa: A miracle herb","volume":"3","author":"A Ahmad","year":"2013","journal-title":"Asian Pac J Trop Biomed"},{"key":"pone.0337970.ref124","article-title":"PubChem 2019 update: improved access to chemical data","volume":"47","author":"S Kim","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"24","key":"pone.0337970.ref125","doi-asserted-by":"crossref","first-page":"4347","DOI":"10.1080\/14786419.2023.2281002","article-title":"Structure-based virtual screening, ADMET analysis, and molecular dynamics simulation of Moroccan natural compounds as candidates for the SARS-CoV-2 inhibitors","volume":"38","author":"O Abchir","year":"2024","journal-title":"Nat Prod Res"},{"key":"pone.0337970.ref126","doi-asserted-by":"crossref","DOI":"10.1016\/j.sciaf.2023.e01745","article-title":"Exploration of Cannabis constituents as potential candidates against diabetes mellitus disease using molecular docking, dynamics simulations and ADMET investigations","volume":"21","author":"O Abchir","year":"2023","journal-title":"Scientific African"},{"issue":"1","key":"pone.0337970.ref127","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1007\/s40278-016-18886-3","article-title":"Neutral-insulin-injection\/insulin-suspension-isophane 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hepatocellular carcinoma cells via AMPK\/mTOR\/p70S6K signaling pathway","volume":"12","author":"L Shui","year":"2020","journal-title":"Aging (Albany NY)"},{"issue":"9","key":"pone.0337970.ref131","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1007\/s11095-005-6250-z","article-title":"Metabolic and pharmacological properties of rutin, a dietary quercetin glycoside, for treatment of inflammatory bowel disease","volume":"22","author":"H Kim","year":"2005","journal-title":"Pharm Res"},{"key":"pone.0337970.ref132","doi-asserted-by":"crossref","first-page":"100361","DOI":"10.1016\/j.chphi.2023.100361","article-title":"Design of a new potent Alzheimer\u2019s disease inhibitor based on QSAR, molecular docking and molecular dynamics investigations","volume":"7","author":"M Khedraoui","year":"2023","journal-title":"Chemical Physics Impact"},{"key":"pone.0337970.ref133","doi-asserted-by":"crossref","DOI":"10.1016\/j.sciaf.2023.e01986","article-title":"The anticoagulant potential of Lippia Alba extract in inhibiting SARS-CoV-2 Mpro: Density functional calculation, molecular docking analysis, and molecular dynamics simulations","volume":"23","author":"I Yamari","year":"2024","journal-title":"Scientific African"},{"key":"pone.0337970.ref134","doi-asserted-by":"crossref","first-page":"101335","DOI":"10.1016\/j.rineng.2023.101335","article-title":"An accurate and universal protein-small molecule batch docking solution using Autodock Vina","volume":"19","author":"X Che","year":"2023","journal-title":"Results in Engineering"},{"issue":"2","key":"pone.0337970.ref135","first-page":"29955","article-title":"Benchmarking different docking protocols for predicting the binding poses of ligands complexed with cyclooxygenase enzymes and screening chemical libraries","volume":"14","author":"S Shamsian","year":"2024","journal-title":"Bioimpacts"},{"key":"pone.0337970.ref136","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":"7","key":"pone.0337970.ref137","doi-asserted-by":"crossref","first-page":"102226","DOI":"10.1016\/j.jksus.2022.102226","article-title":"Unsymmetrical aromatic disulfides as SARS-CoV-2 Mpro inhibitors: Molecular docking, molecular dynamics, and ADME scoring investigations","volume":"34","author":"S Chtita","year":"2022","journal-title":"J King Saud Univ Sci"},{"issue":"26","key":"pone.0337970.ref138","doi-asserted-by":"crossref","DOI":"10.1002\/slct.202301092","article-title":"Structure\u2010Based Virtual Screening, ADMET analysis, and Molecular Dynamics Simulation of Moroccan Natural Compounds as Candidates \u03b1\u2010Amylase Inhibitors","volume":"8","author":"O Abchir","year":"2023","journal-title":"ChemistrySelect"},{"issue":"2","key":"pone.0337970.ref139","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1002\/bkcs.12449","article-title":"2D\u2010QSAR and molecular docking studies of carbamate derivatives to discover novel potent anti\u2010butyrylcholinesterase agents for Alzheimer\u2019s disease treatment","volume":"43","author":"H Nour","year":"2021","journal-title":"Bulletin Korean Chem Soc"},{"issue":"1","key":"pone.0337970.ref140","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1021\/ci100275a","article-title":"Assessing the performance of the MM\/PBSA and MM\/GBSA methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations","volume":"51","author":"T Hou","year":"2011","journal-title":"J Chem Inf Model"},{"issue":"2","key":"pone.0337970.ref141","doi-asserted-by":"crossref","first-page":"74","DOI":"10.4103\/0976-500X.81895","article-title":"Toxicological screening","volume":"2","author":"S Parasuraman","year":"2011","journal-title":"J Pharmacol Pharmacother"},{"issue":"4574","key":"pone.0337970.ref142","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1126\/science.218.4574.747","article-title":"Role of frontier orbitals in chemical reactions","volume":"218","author":"K Fukui","year":"1982","journal-title":"Science"},{"issue":"38","key":"pone.0337970.ref143","doi-asserted-by":"crossref","first-page":"24891","DOI":"10.1021\/acsomega.1c03736","article-title":"Theoretical Studies on the Molecular Properties, Toxicity, and Biological Efficacy of 21 New Chemical Entities","volume":"6","author":"R Srivastava","year":"2021","journal-title":"ACS Omega"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0337970","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T17:42:36Z","timestamp":1773250956000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0337970"}},"subtitle":[],"editor":[{"given":"Gayathiri","family":"Ekambaram","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,3,11]]},"references-count":143,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0337970","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,11]]}}}