{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:18:10Z","timestamp":1790209090776,"version":"4.1.0"},"reference-count":84,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF)","award":["RS-2023-00276023"],"award-info":[{"award-number":["RS-2023-00276023"]}]},{"name":"National Research Foundation of Korea (NRF)","award":["NRF-2021R1I1A306005711"],"award-info":[{"award-number":["NRF-2021R1I1A306005711"]}]},{"name":"Ministry of Education","award":["RS-2023-00276023"],"award-info":[{"award-number":["RS-2023-00276023"]}]},{"name":"Ministry of Education","award":["NRF-2021R1I1A306005711"],"award-info":[{"award-number":["NRF-2021R1I1A306005711"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Snakebite envenoming is a significant health threat, particularly in tropical regions, causing substantial morbidity and mortality. Traditional treatments, including antivenom therapy, have limitations and associated risks. This research aims to discover novel phytochemical antidotes for snakebites, specifically targeting the western diamondback rattlesnake (Crotalus atrox) venom metalloproteinase Atrolysin. Utilizing pharmacoinformatic techniques such as molecular docking, high-throughput ligand screening, pharmacophore mapping, pharmacokinetic profiling, and molecular dynamics (MD) simulations, we analyzed phytochemicals from the Indian Medicinal Plants, Phytochemistry And Therapeutics (IMPPAT) database alongside well-known nine metalloproteinase inhibitors from the PubChem database. From an initial set of 17,967 compounds, 4708 unique compounds were identified for further study. These compounds were evaluated based on drug likeness, molecular descriptors, ADME properties, and toxicity profiles. Binding site predictions and molecular docking identified key interacting residues and binding energies, highlighting several promising compounds. Density functional theory (DFT) analysis provided insights into these compounds\u2019 electronic properties and stability. MD simulations assessed the dynamic stability of protein-ligand complexes using parameters such as RMSD, RMSF, the radius of gyration, and hydrogen bond interactions. This study identified top candidates, including CID5291, IMPHY001495, IMPHY014737, IMPHY008983, IMPHY008176, and IMPHY003833, based on their favorable binding energies, interaction forces, and structural stability. These findings suggest that the selected phytochemicals have the potential to serve as effective alternatives to traditional antivenom treatments, offering a promising avenue for further research and development in snakebite management.<\/jats:p>","DOI":"10.3390\/ijms252312675","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T04:02:18Z","timestamp":1732593738000},"page":"12675","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Indian Medicinal Plant-Derived Phytochemicals as Potential Antidotes for Snakebite: A Pharmacoinformatic Study of Atrolysin Inhibitors"],"prefix":"10.3390","volume":"25","author":[{"given":"Deva Asirvatham","family":"Ravi","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Du Hyeon","family":"Hwang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Republic of Korea"},{"name":"Institute of Animal Medicine, Gyeongsang National University, Jinju 52828, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramachandran Loganathan","family":"Mohan Prakash","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5114-5096","authenticated-orcid":false,"given":"Changkeun","family":"Kang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Republic of Korea"},{"name":"Institute of Animal Medicine, Gyeongsang National University, Jinju 52828, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3356-3072","authenticated-orcid":false,"given":"Euikyung","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Republic of Korea"},{"name":"Institute of Animal Medicine, Gyeongsang National University, Jinju 52828, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s40409-017-0127-6","article-title":"Snakebite Envenomation Turns Again into a Neglected Tropical Disease!","volume":"23","author":"Chippaux","year":"2017","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Martins, S.B., Bolon, I., Chappuis, F., Ray, N., Alcoba, G., Ochoa, C., Sharma, S.K., Nkwescheu, A.S., Wanda, F., and Durso, A.M. (2019). Snakebite and Its Impact in Rural Communities: The Need for a One Health Approach. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007608"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17063","DOI":"10.1038\/nrdp.2017.63","article-title":"Snakebite Envenoming","volume":"3","author":"Calvete","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S0140-6736(18)31224-8","article-title":"Vulnerability to Snakebite Envenoming: A Global Mapping of Hotspots","volume":"392","author":"Longbottom","year":"2018","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kasturiratne, A., Wickremasinghe, A.R., De Silva, N., Gunawardena, N.K., Pathmeswaran, A., Premaratna, R., Savioli, L., Lalloo, D.G., and De Silva, H.J. (2008). The Global Burden of Snakebite: A Literature Analysis and Modelling Based on Regional Estimates of Envenoming and Deaths. PLoS Med., 5.","DOI":"10.1371\/journal.pmed.0050218"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"107242","DOI":"10.1016\/j.toxicon.2023.107242","article-title":"Kaempferol from Moringa Oleifera Demonstrated Potent Antivenom Activities via Inhibition of Metalloproteinase and Attenuation of Bitis Arietans Venom\u2013Induced Toxicities","volume":"233","author":"Ajisebiola","year":"2023","journal-title":"Toxicon"},{"key":"ref_7","unstructured":"World Health Organization (2019). Snakebite Envenoming: A Strategy for Prevention and Control, World Health Organization."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/jbt.20404","article-title":"Inactivation of Crotalus Atrox Venom Hemorrhagic Activity by Direct Current Exposure Using Hens\u2019 Egg Assay","volume":"25","author":"Calzia","year":"2011","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1016\/j.toxicon.2009.01.038","article-title":"Experimental Pathology of Local Tissue Damage Induced by Bothrops Asper Snake Venom","volume":"54","author":"Rucavado","year":"2009","journal-title":"Toxicon"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.toxicon.2005.02.030","article-title":"Snake Venoms and Coagulopathy","volume":"45","author":"White","year":"2005","journal-title":"Toxicon"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1006\/exmp.1995.1042","article-title":"Local Tissue Damage Induced by BaP1, a Metalloproteinase Isolated from Bothrops Asper (Terciopelo) Snake Venom","volume":"63","author":"Rucavado","year":"1995","journal-title":"Exp. Mol. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3042","DOI":"10.1046\/j.1432-1327.2001.02199.x","article-title":"BJ46a, a Snake Venom Metalloproteinase Inhibitor","volume":"268","author":"Valente","year":"2001","journal-title":"Eur. J. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Adri\u00e3o, A.A.X., dos Santos, A.O., de Lima, E.J.S.P., Maciel, J.B., Paz, W.H.P., da Silva, F.M.A., Pucca, M.B., Moura-da-Silva, A.M., Monteiro, W.M., and Sartim, M.A. (2022). Plant-Derived Toxin Inhibitors as Potential Candidates to Complement Antivenom Treatment in Snakebite Envenomations. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.842576"},{"key":"ref_14","first-page":"143","article-title":"Studies on effect of salt stress on some medicinal plants","volume":"2","author":"Kumari","year":"2012","journal-title":"Int. J. Comput. Eng. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.phymed.2004.01.012","article-title":"Evaluation of the Effect of Aqueous Extract of Croton Urucurana Baillon (Euphorbiaceae) on the Hemorrhagic Activity Induced by the Venom of Bothrops Jararaca, Using New Techniques to Quantify Hemorrhagic Activity in Rat Skin","volume":"12","author":"Esmeraldino","year":"2005","journal-title":"Phytomedicine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1016\/j.jep.2014.08.002","article-title":"Inhibition of the Toxic Effects of Bothrops Asper Venom by Pinostrobin, a Flavanone Isolated from Renealmia alpinia (Rottb.) MAAS","volume":"155","author":"Benjumea","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_17","first-page":"60","article-title":"Implications of Phytochemicals in Snakebite Management: Present Status and Future Prospective","volume":"33","author":"Urs","year":"2014","journal-title":"Toxin Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2556","DOI":"10.2174\/156802611797633410","article-title":"Daboia Russelli Venom Hyaluronidase: Purification, Characterization and Inhibition by \u03b2-3-(3-Hydroxy-4-Oxopyridyl) \u03b1-Amino-Propionic Acid","volume":"11","author":"Mahadeswaraswamy","year":"2011","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/0041-0101(87)90156-5","article-title":"Interaction of Phospholipase A2 from Vipera Russelli Venom with Aristolochic Acid: A Circular Dichroism Study","volume":"25","author":"Vishwanath","year":"1987","journal-title":"Toxicon"},{"key":"ref_20","first-page":"342","article-title":"Studies on Snake Venom Enzymes: Part II - Partial Characterization of ATPases from Russell\u2019s Viper (Vipera russelli) Venom and Their Interaction with Potassium Gymnemate","volume":"19","year":"1982","journal-title":"Indian. J. Biochem. Biophys."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1021\/acsomega.2c04837","article-title":"Computational Exploration of Anti-Cancer Potential of Flavonoids against Cyclin-Dependent Kinase 8: An In Silico Molecular Docking and Dynamic Approach","volume":"8","author":"Rathod","year":"2023","journal-title":"ACS Omega"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/aps.2012.109","article-title":"Computational Drug Discovery","volume":"33","author":"Lu","year":"2012","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3292","DOI":"10.2174\/1381612825666190903155935","article-title":"In-Silico Modeling in Drug Metabolism and Interaction: Current Strategies of Lead Discovery","volume":"25","author":"Roy","year":"2019","journal-title":"Curr. Pharm. Des."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Brogi, S., Ramalho, T., Kuca, K., Medina-Franco, J.L., and Valko, M. (2020). In Silico Methods for Drug Design and Discovery. Front. Chem., 8.","DOI":"10.3389\/fchem.2020.00612"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.csbj.2016.04.004","article-title":"Computational Approaches in Target Identification and Drug Discovery","volume":"14","author":"Katsila","year":"2016","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1590\/S0074-02762005000900031","article-title":"Inflammatory Effects of Snake Venom Metalloproteinases","volume":"100","author":"Teixeira","year":"2005","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"De Almeida, M.T., Freitas-De-Sousa, L.A., Colombini, M., Gimenes, S.N.C., Kitano, E.S., Faquim-Mauro, E.L., Serrano, S.M.T., and Moura-Da-Silva, A.M. (2020). Inflammatory Reaction Induced by Two Metalloproteinases Isolated from Bothrops Atrox Venom and by Fragments Generated from the Hydrolysis of Basement Membrane Components. Toxins, 12.","DOI":"10.3390\/toxins12020096"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Larr\u00e9ch\u00e9, S., Chippaux, J.P., Chevillard, L., Math\u00e9, S., R\u00e9si\u00e8re, D., Siguret, V., and M\u00e9garbane, B. (2021). Bleeding and Thrombosis: Insights into Pathophysiology of Bothrops Venom-Related Hemostasis Disorders. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179643"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1111\/bjh.14591","article-title":"Haemotoxic Snake Venoms: Their Functional Activity, Impact on Snakebite Victims and Pharmaceutical Promise","volume":"177","author":"Slagboom","year":"2017","journal-title":"Br. J. Haematol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.1111\/j.1742-4658.2008.06466.x","article-title":"Insights into and Speculations about Snake Venom Metalloproteinase (SVMP) Synthesis, Folding and Disulfide Bond Formation and Their Contribution to Venom Complexity","volume":"275","author":"Fox","year":"2008","journal-title":"FEBS J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.2174\/1568026611208011095","article-title":"Molecular Mechanisms Regulating Matrix Metalloproteinases","volume":"12","author":"Piperi","year":"2012","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.toxicon.2011.01.006","article-title":"Haemostatically Active Proteins in Snake Venoms","volume":"57","author":"Sajevic","year":"2011","journal-title":"Toxicon"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4544","DOI":"10.1111\/j.1742-4658.2011.08115.x","article-title":"Enzymatic Toxins from Snake Venom: Structural Characterization and Mechanism of Catalysis","volume":"278","author":"Kang","year":"2011","journal-title":"FEBS J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.toxicon.2012.09.003","article-title":"The Long Road of Research on Snake Venom Serine Proteinases","volume":"62","author":"Serrano","year":"2013","journal-title":"Toxicon"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.bbapap.2011.04.009","article-title":"Snake Venom Metalloproteinases: Structure, Function and Relevance to the Mammalian ADAM\/ADAMTS Family Proteins","volume":"1824","author":"Takeda","year":"2012","journal-title":"Biochim. Biophys. Acta (BBA)-Proteins Proteom."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1021\/np960355p","article-title":"Ehretianone, a Novel Quinonoid Xanthene from Ehretia Buxifolia with Antisnake Venom Activity","volume":"59","author":"Selvanayagam","year":"1996","journal-title":"J. Nat. Prod."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"G\u00f3mez-Betancur, I., Gogineni, V., Salazar-Ospina, A., and Le\u00f3n, F. (2019). Perspective on the Therapeutics of Anti-Snake Venom. Molecules, 24.","DOI":"10.3390\/molecules24183276"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1080\/10496475.2014.961627","article-title":"In Vitro Anti-Snake Venom Properties of Carisssa Spinarum Linn Leaf Extracts","volume":"21","author":"Janardhan","year":"2015","journal-title":"J. Herbs Spices Med. Plants"},{"key":"ref_39","first-page":"153","article-title":"Traditional Use of Plants against Snakebite in Indian Subcontinent: A Review of the Recent Literature","volume":"9","author":"Dey","year":"2012","journal-title":"Afr. J. Tradit. Complement. Altern. Med."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Owuor, B.O., and Kisangau, D.P. (2006). Kenyan Medicinal Plants Used as Antivenin: A Comparison of Plant Usage. J. Ethnobiol. Ethnomed., 2.","DOI":"10.1186\/1746-4269-2-7"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.bbapap.2011.03.002","article-title":"Identification of a Novel and Potent Inhibitor of Phospholipase A2 in a Medicinal Plant: Crystal Structure at 1.93 \u00c5 and Surface Plasmon Resonance Analysis of Phospholipase A2 Complexed with Berberine","volume":"1814","author":"Chandra","year":"2011","journal-title":"Biochim. Biophys. Acta (BBA)-Proteins Proteom."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/S0003-9861(02)00527-1","article-title":"Purification and Characterization of a Glycoprotein Inhibitor of Toxic Phospholipase from Withania Somnifera","volume":"408","author":"Deepa","year":"2002","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.toxicon.2006.06.017","article-title":"Anticoagulant Effect of Naja Naja Venom 5\u2032nucleotidase: Demonstration through the Use of Novel Specific Inhibitor, Vanillic Acid","volume":"48","author":"Dhananjaya","year":"2006","journal-title":"Toxicon"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jep.2005.11.031","article-title":"Daboia Russellii and Naja Kaouthia Venom Neutralization by Lupeol Acetate Isolated from the Root Extract of Indian Sarsaparilla Hemidesmus Indicus R.Br","volume":"106","author":"Chatterjee","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"602","DOI":"10.3109\/13880209.2010.537828","article-title":"Evaluation of Anti-Inflammatory Activity of Derivatives from Aerial Parts of Baccharis Uncinella","volume":"49","author":"Zalewski","year":"2011","journal-title":"Pharm. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41573-020-00114-z","article-title":"Natural Products in Drug Discovery: Advances and Opportunities","volume":"20","author":"Atanasov","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0378-8741(99)00197-X","article-title":"Snakebites and Ethnobotany in the Northwest Region of Colombia. Part II: Neutralization of Lethal and Enzymatic Effects of Bothrops Atrox Venom","volume":"71","author":"Otero","year":"2000","journal-title":"J. Ethnopharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural Products as Sources of New Drugs over the Nearly Four Decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1007\/s00894-011-0994-7","article-title":"In Silico Identification of Viper PhospholipaseA2 Inhibitors: Validation by in Vitro, in Vivo Studies","volume":"17","author":"Nargotra","year":"2011","journal-title":"J. Mol. Model."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"76","DOI":"10.51847\/HIrDcdPCGL","article-title":"Screening of Phytochemicals Against Snake Venom Metalloproteinase: Molecular Docking and Simulation Based Computational Approaches","volume":"13","author":"Alshammari","year":"2022","journal-title":"Arch. Pharm. Pr."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Preciado, L.M., Comer, J., N\u00fa\u00f1ez, V., Rey-S\u00faarez, P., and Perea\u00f1ez, J.A. (2018). Inhibition of a Snake Venom Metalloproteinase by the Flavonoid Myricetin. Mol. A J. Synth. Chem. Nat. Prod. Chem., 23.","DOI":"10.3390\/molecules23102662"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.saa.2012.11.001","article-title":"Experimental and DFT Studies on the Antioxidant Activity of a C-Glycoside from Rhynchosia Capitata","volume":"103","author":"Praveena","year":"2013","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.saa.2011.02.042","article-title":"Antioxidant Behavior of Mearnsetin and Myricetin Flavonoid Compounds\u2014A DFT Study","volume":"79","author":"Sadasivam","year":"2011","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s42269-024-01261-8","article-title":"Exploring Compound Suitability and Employing DFT Calculations, Molecular Docking, and Dynamics Simulation to Investigate Potent Compounds from Podophyllum Medicinal Plants for Breast Cancer Therapy","volume":"48","author":"Mande","year":"2024","journal-title":"Bull. Natl. Res. Cent."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1080\/00268976.2011.556576","article-title":"A Comparative DFT Study on the Antioxidant Activity of Apigenin and Scutellarein Flavonoid Compounds","volume":"109","author":"Kandasamy","year":"2011","journal-title":"Mol. Phys."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"107838","DOI":"10.1016\/j.toxicon.2024.107838","article-title":"Exploring the Inhibitory Potential of Phytochemicals from Vernonia Glaberrima Leaves against Snake Venom Toxins through Computational Simulation and Experimental Validation","volume":"247","author":"Yusuf","year":"2024","journal-title":"Toxicon"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"100435","DOI":"10.1016\/j.prmcm.2024.100435","article-title":"MM\/GB(PB)SA Integrated with Molecular Docking and ADMET Approach to Inhibit the Fat-Mass-and-Obesity-Associated Protein Using Bioactive Compounds Derived from Food Plants Used in Traditional Chinese Medicine","volume":"11","author":"Mandal","year":"2024","journal-title":"Pharmacol. Res.-Mod. Chin. Med."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Mangat, H.K., Rani, M., Pathak, R.K., Yadav, I.S., Utreja, D., Chhuneja, P.K., and Chhuneja, P. (2022). Virtual Screening, Molecular Dynamics and Binding Energy-MM-PBSA Studies of Natural Compounds to Identify Potential EcR Inhibitors against Bemisia Tabaci Gennadius. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0261545"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Salaria, P., and Reddy, M.A. (2024). Network Pharmacology Approach to Identify the Calotropis Phytoconstituents\u2019 Potential Epileptic Targets and Evaluation of Molecular Docking, MD Simulation, and MM-PBSA Performance. Chem. Biodivers., 21.","DOI":"10.1002\/cbdv.202400255"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/j.jsps.2020.04.010","article-title":"In Vitro and in Vivo Inhibitory Effects of Tabernaemontana Alternifolia against Naja Naja Venom","volume":"28","author":"Vineetha","year":"2020","journal-title":"Saudi Pharm. J.  SPJ"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jep.2017.09.015","article-title":"The Effects of Cissampelos Pareira Extract on Envenomation Induced by Bothropsdiporus Snake Venom","volume":"212","author":"Ricciardi","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"116","DOI":"10.22270\/jddt.v9i4.3116","article-title":"Evaluation of in Vitro Anti Snake Venom Activity of Justicia Adhatoda Leaves Extract against Russell\u2019s Viper Snake Venom","volume":"9","author":"Ramaswamy","year":"2019","journal-title":"J. Drug Deliv. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e18050","DOI":"10.1590\/s2175-97902019000418050","article-title":"Neutralizing Potential of Rauvolfia Serpentina Root Extract against Naja Naja Venom","volume":"56","author":"Sivaraman","year":"2020","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_64","first-page":"1","article-title":"Medicinal Plants for the Treatment of Local Tissue Damage Induced by Snake Venoms: An Overview from Traditional Use to Pharmacological Evidence","volume":"2017","author":"Zucolotto","year":"2017","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/j.toxrep.2018.10.004","article-title":"Ameliorating Effect of Alstonia Scholaris L. Bark Extract on Histopathological Changes Following Viper Envenomation in Animal Models","volume":"5","author":"Ghosh","year":"2018","journal-title":"Toxicol. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"8827","DOI":"10.1021\/acsomega.3c00156","article-title":"IMPPAT 2.0: An Enhanced and Expanded Phytochemical Atlas of Indian Medicinal Plants","volume":"8","author":"Mohanraj","year":"2023","journal-title":"ACS Omega"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Vivek-Ananth, R.P., Rana, A., Rajan, N., Biswal, H.S., and Samal, A. (2020). In Silico Identification of Potential Natural Product Inhibitors of Human Proteases Key to SARS-CoV-2 Infection. Molecules, 25.","DOI":"10.3390\/molecules25173822"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"W5","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":"Xiong","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Schyman, P., Liu, R., Desai, V., and Wallqvist, A. (2017). VNN Web Server for ADMET Predictions. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00889"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1080\/17460441.2019.1581170","article-title":"DataWarrior: An Evaluation of the Open-Source Drug Discovery Tool","volume":"14","author":"Naveja","year":"2019","journal-title":"Expert. Opin. Drug Discov."},{"key":"ref_71","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":"Banck","year":"2011","journal-title":"J. Cheminform"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera--a Visualization System for Exploratory Research and Analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"8447","DOI":"10.1073\/pnas.91.18.8447","article-title":"Structural Interaction of Natural and Synthetic Inhibitors with the Venom Metalloproteinase, Atrolysin C (Form d)","volume":"91","author":"Zhang","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.csbj.2020.02.008","article-title":"Exploring the Computational Methods for Protein-Ligand Binding Site Prediction","volume":"18","author":"Zhao","year":"2020","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"146","DOI":"10.2174\/157340911795677602","article-title":"Molecular Docking: A Powerful Approach for Structure-Based Drug Discovery","volume":"7","author":"Meng","year":"2011","journal-title":"Curr. Comput. Aided Drug Des."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"W443","DOI":"10.1093\/nar\/gkv315","article-title":"PLIP: Fully Automated Protein\u2013Ligand Interaction Profiler","volume":"43","author":"Salentin","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Yadalam, P.K., Varatharajan, K., Rajapandian, K., Chopra, P., Arumuganainar, D., Nagarathnam, T., Sohn, H., and Madhavan, T. (2021). Antiviral Essential Oil Components Against SARS-CoV-2 in Pre-Procedural Mouth Rinses for Dental Settings During COVID-19: A Computational Study. Front. Chem., 9.","DOI":"10.3389\/fchem.2021.642026"},{"key":"ref_78","first-page":"5150","article-title":"Molecular Orbital Studies (Hardness, Chemical Potential, Electro Negativity and Electrophilicity) of TTFs Conjugated between 1, 3-Dithiole","volume":"5","author":"Abbaz","year":"2018","journal-title":"Int. J. Adv. Res. Sci. Eng. Technol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"112117","DOI":"10.1016\/j.mcat.2022.112117","article-title":"Density Functional Theory Study of the Selective Oxidation of 5-Hydroxymethylfurfural (HMF) to 5-Hydroxymethyl-2-Furancarboxylic Acid (HMFCA) on the Silver Oxide Surface (001)","volume":"519","author":"Celaya","year":"2022","journal-title":"Mol. Catal."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Rajendran, B.K., Xavier Suresh, M., Bhaskaran, S.P., Harshitha, Y., Gaur, U., and Kwok, H.F. (2018). Pharmacoinformatic Approach to Explore the Antidote Potential of Phytochemicals on Bungarotoxin from Indian Krait, Bungarus Caeruleus. Comput. Struct. Biotechnol. J., 16.","DOI":"10.1016\/j.csbj.2018.10.005"},{"key":"ref_81","first-page":"8539918","article-title":"Computational Study of the Phytochemical Constituents from Uncaria Tomentosa Stem Bark against SARS-CoV-2 Omicron Spike Protein","volume":"2022","author":"Saleh","year":"2022","journal-title":"J. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Asirvatham, R.D., Hwang, D.H., Prakash, R.L.M., Kang, C., and Kim, E. (2023). Pharmacoinformatic Investigation of Silymarin as a Potential Inhibitor against Nemopilema Nomurai Jellyfish Metalloproteinase Toxin-like Protein. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24108972"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Himaja, K., Veerapandiyan, K., and Usha, B. (2024). Aromatase inhibitors identified from Saraca asoca to treat infertility in women with polycystic ovary syndrome via in silico and in vivo studies. J. Biomol. Struct. Dyn., 1\u201316.","DOI":"10.1080\/07391102.2024.2310793"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1021\/ci500020m","article-title":"G-Mmpbsa\u2014A GROMACS Tool for High-Throughput MM-PBSA Calculations","volume":"54","author":"Kumari","year":"2014","journal-title":"J. Chem. Inf. Model."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/23\/12675\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:39:32Z","timestamp":1760114372000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/23\/12675"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,26]]},"references-count":84,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["ijms252312675"],"URL":"https:\/\/doi.org\/10.3390\/ijms252312675","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,26]]}}}