Viola stocksii: A rich source of antioxidant and anti-inflammatory flavonoid glycosides with converged therapeutic potential against SARS-CoV-2 MPro, spike trimer, and surface glycoproteins
Roshan Zamir, Shanza Munir, Humaira Yasmeen Gondal, Muhammad Nisar, Sami A Al-Hussain, Ahmed Abbaskhan, Zain M Cheema, Magdi E A Zaki, M Iqbal Choudhary
Food Bioscience, doi:10.1016/j.fbio.2024.105095
This research presents the first comprehensive investigation into the phytochemical and nutraceutical properties of Viola stocksii. The study aimed to identify the therapeutic efficacy and bioactive constituents of this medicinal herb, traditionally used as an herbal tea for managing respiratory and abdominal issues in remote areas of Pakistan. The therapeutic efficacy of the plant was assessed as an anti-oxidant-rich health tonic coupled with anti-inflammatory and immunomodulatory activities against COVID-19 and its evolving variants. The study involved sequential extraction, bio-assay guided fractionation, isolation, characterization, and biological evaluation. Preliminary in vitro studies have demonstrated that polar fractions of the plant possess significant antioxidant and antiinflammatory potential. A diverse combination of chromatographic techniques (Diaion resin HP-20, Sephadex LH-20, ODS-C18, and RP-HPLC) facilitated the purification of active constituents of the plant. Comprehensive analysis of NMR ( 1 H, 13 C, and 2D NMR) and mass (EIMS, HR-EIMS, and FAB-HRMS) spectral data lead to characterize the isolated compounds (1-4) as flavonoid glycosides. Results from in vitro and in-silico evaluations revealed that the isolated glycosides exhibit high antioxidant, antiinflammatory, and immunomodulatory activities, which synergistically show promising potential in combating SARS-CoV-2 variants. Besides M Pro , therapeutic potential against two unexplored proteins i.e. the spike trimer (7WZ1) and surface glycoproteins (7QTJ) was studied for the first time. Kaempferol (KamGluαRh) and quercetin (QurGluαRh) carrying rutinoside, were identified as the most active constituents of the plant, with the highest binding affinities in the range of -10 to -13 kcal/mol. Ten distinct active regions were explored on the spike trimer, including strong binding affinity with the essential RBD region, spike head, and tail of the protein. MD simulation validated the stability of M pro -KamGluαRh and M pro -QurGluαRh complexes evidenced by an average RMSD of 0.2 nm led to the mechanistic understanding of M pro inhibition. ADMET and pharmacokinetic studies authenticated the therapeutic ability and drug-likeness profiling of all extracted compounds. Results revealed the beneficial role of glycosides in boosting the medicinal effectiveness of flavonoids and the potential of Viola stocksii as an immunity booster against respiratory infections like COVID-19.
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi. org/10.1016/j.fbio.2024.105095 .
References
Abraham, Murtola, Schulz, Páll, Smith et al., Gromacs: High performance molecular simulations through multi-level parallelism from laptops to supercomputers, SoftwareX,
doi:10.1016/j.softx.2015.06.001Abusaliya, Ha, Bhosale, Kim, Park et al., Glycosidic flavonoids and their potential applications in cancer research: A review, Molecular & Cellular Toxicology,
doi:10.1007/s13273-021-00178-xAhmed, Ahmad, Yaseen, Zafar, Rashid et al., Quality assurance and authentication of herbal drug (Argyrolobium roseum and Viola stocksii) through comparative light and scanning electron microscopy, Microscopy Research and Technique,
doi:10.1002/jemt.23560Akbari, Baghaei-Yazdi, Bahmaie, Mahdavi Abhari, The role of plant-derived natural antioxidants in reduction of oxidative stress, BioFactors,
doi:10.1002/biof.1831Banerjee, Eckert, Schrey, Preissner, ProTox-II: A webserver for the prediction of toxicity of chemicals, Nucleic Acids Research,
doi:10.1093/nar/gky318Bentivenha, Canassa, Baldin, Borguini, Lima et al., Role of the rutin and genistein flavonoids in soybean resistance to Piezodorus guildinii (Hemiptera: Pentatomidae), Arthropod-plant interactions,
doi:10.1007/s11829-017-9578-5Brindha, Role of phytochemicals as immunomodulatory agents: A review, International Journal of Green Pharmacy,
doi:10.22377/ijgp.v10i1.600Bzówka, Mitusińska, Raczyńska, Samol, Tuszyński et al., Structural and evolutionary analysis indicate that the SARS-CoV-2 Mpro is a challenging target for small-molecule inhibitor design, International Journal of Molecular Sciences,
doi:10.3390/ijms21093099Báez-Santos, John, Mesecar, The SARS-coronavirus papainlike protease: Structure, function and inhibition by designed antiviral compounds, Antiviral Research,
doi:10.1016/j.antiviral.2014.12.015Castañeda, Dulcey, Martínez, Flavonoid glycosides from Siparuna gigantotepala leaves and their antioxidant activity, Chemical and Pharmaceutical Bulletin,
doi:10.1248/cpb.c15-00788Chandra, Kohli, Prasad, Bisht, Punetha et al., Phytochemical and ethnomedicinal uses of family Violaceae, Curr. Res. Chem,
doi:10.3923/crc.2015.44.52Chaves, Lima, Fintelman-Rodrigues, Sacramento, De Freitas et al., Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 replication by targeting its proteases, International Journal of Biological Macromolecules,
doi:10.1016/j.ijbiomac.2022.09.204Chaves, Sacramento, Ferreira, Mattos, Fintelman-Rodrigues et al., Atazanavir is a competitive inhibitor of SARS-CoV-2 Mpro, impairing variants replication in vitro and in vivo, Pharmaceuticals,
doi:10.3390/ph15010021Cheema, Nisar, Gondal, Alhussain, Zaki et al., New benzotriazole-derived α-substituted hemiaminal ethers with enhanced cholinesterase inhibition activity: Synthesis, structural, and biological evaluations, Journal of Saudi Chemical Society,
doi:10.1016/j.jscs.2023.101746Cheng, Li, Zhou, Shen, Wu et al., admetSAR: a comprehensive source and free tool for assessment of chemical ADMET properties, ACS Publications,
doi:10.1021/ci300367aCherrak, Merzouk, Mokhtari-Soulimane, Potential bioactive glycosylated flavonoids as SARS-CoV-2 main protease inhibitors: A molecular docking study,
doi:10.1371/journal.pone.0240653Chuang, Lin, Lin, Wang, Chen et al., Elucidating the skin delivery of aglycone and glycoside flavonoids: How the structures affect cutaneous absorption, Nutrients,
doi:10.3390/nu9121304Conti, Younes, Coronavirus COV-19/SARS-CoV-2 affects women less than men: Clinical response to viral infection, Journal of Biological Regulators & Homeostatic Agents,
doi:10.23812/Editorial-Conti-3Da Silva, Da Silva, De Oliveira, Costa, Koolen et al., Flavonoid glycosides and their putative human metabolites as potential inhibitors of the SARS-CoV-2 main protease (Mpro) and RNA-dependent RNA polymerase (RdRp), 115. Memórias do Instituto Oswaldo Cruz,
doi:10.1590/0074-02760200207Daina, Michielin, Zoete, SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Scientific Reports,
doi:10.1038/srep42717Desingu, Nagarajan, Dhama, Emergence of Omicron third lineage BA. 3 and its importance, Journal of Medical Virology
Ding, Zhao, Huang, Du, Dong et al., Regulation of ROS in transmissible gastroenteritis virus-activated apoptotic signaling, Biochemical and biophysical research communications,
doi:10.1016/j.bbrc.2013.10.164Diniz, Bezerra Filho, Fielding, Sousa, Natural antioxidants: A review of studies on human and animal coronavirus. Oxidative Medicine and Cellular Longevity,
doi:10.1155/2020/3173281Drwal, Banerjee, Dunkel, Wettig, Preissner, ProTox: A web server for the in silico prediction of rodent oral toxicity, Nucleic Acids Research,
doi:10.1093/nar/gku401El-Hadary, Sulieman, El-Shorbagy, Comparative effects of hibiscus leaves and potato peel extracts on characteristics of fermented orange juice, Journal of food quality and hazards control,
doi:10.18502/jfqhc.10.1.11988El-Hadary, Sulieman, El-Shorbagy, Comparative the antioxidants characteristics of orange and potato peels extracts under differences in pressure and conventional extractions,
doi:10.34302/crpjfst/2022.14.1.13Esakandari, Nabi-Afjadi, Fakkari-Afjadi, Farahmandian, Miresmaeili et al., A comprehensive review of COVID-19 characteristics, Biological Procedures Online,
doi:10.1186/s12575-020-00128-2Fathi, Delazar, Amiri, Extraction of flavonoids and quantification of rutin from waste tobacco leaves
Ferraz, Carvalho, Manchope, Artero, Rasquel-Oliveira et al., Therapeutic potential of flavonoids in pain and inflammation: Mechanisms of action, pre-clinical and clinical data, and pharmaceutical development, Molecules,
doi:10.3390/molecules25030762Franzoni, Scarfò, Guidotti, Fusi, Asomov et al., Oxidative stress and cognitive decline: The neuroprotective role of natural antioxidants, Frontiers in Neuroscience,
doi:10.3389/fnins.2021.729757Freitas, Durie, Murray, Longo, Miller et al., Characterization and noncovalent inhibition of the deubiquitinase and deISGylase activity of SARS-CoV-2 papain-like protease, ACS Infectious Diseases,
doi:10.1021/acsinfecdis.0c00168Gadallah, Yousuf, Jabeen, Swilam, Khalifa et al., Anti-inflammatory principles from tamarix aphylla L.: A bioassay-guided fractionation study, Molecules,
doi:10.3390/molecules25132994Ganeshpurkar, Saluja, In silico interaction of hesperidin with some immunomodulatory targets: A docking analysis, Indian Journal of Biochemistry & Biophysics
Godinho, Soengas, Silva, Therapeutic potential of glycosyl flavonoids as anti-coronaviral agents, Pharmaceuticals,
doi:10.3390/ph14060546Han, Fu, Deng, Luo, Xiang et al., Immunomodulatory potential of flavonoids for the treatment of autoimmune diseases and tumour, Scandinavian Journal of Immunology,
doi:10.1111/sji.13106Harborne, Mabry, The flavonoids: Advances in research
Hasler, Gross, Meier, Sticher, Helfand et al., Chemiluminescence response of human natural killer cells. I. The relationship between target cell binding, chemiluminescence, and cytolysis, The Journal of experimental medicine,
doi:10.1084/jem.156.2.492Hussain, Azam, Eldarrat, Alkskas, Mayoof et al., Anti-inflammatory, analgesic and molecular docking studies of Lanostanoic acid 3-O-α-D-glycopyranoside isolated from Helichrysum stoechas, Arabian Journal of Chemistry,
doi:10.1016/j.arabjc.2020.11.004Ibrahim, Mohamed, Abdelrahman, Allemailem, Moustafa et al., Rutin and flavone analogs as prospective SARS-CoV-2 main protease inhibitors: In silico drug discovery study, Journal of Molecular Graphics and Modelling,
doi:10.1016/j.jmgm.2021.107904Inomata, Terahara, Kitajima, Kokubugata, Iwashina, Flavones and anthocyanins from the leaves and flowers of Japanese Ajuga species (Lamiaceae), Biochemical Systematics and Ecology,
doi:10.1016/j.bse.2013.08.004Ivanović, Rančić, Arsić, Pavlović, Lipinski's rule of five, famous extensions and famous exceptions, Popular Scientific Article
Jucá, Cysne Filho, De Almeida, Mesquita, Barriga et al., Flavonoids: Biological activities and therapeutic potential, Natural Product Research,
doi:10.1080/14786419.2018.1493588Khaerunnisa, Kurniawan, Awaluddin, Suhartati, Soetjipto, Potential inhibitor of COVID-19 main protease (Mpro) from several medicinal plant compounds by molecular docking study, Preprints
Klemm, Ebert, Calleja, Allison, Richardson et al., Mechanism and inhibition of the papain-like protease, PLpro, of SARS-CoV-2, The EMBO journal,
doi:10.15252/embj.2020106275Klimoszek, Jeleń, Dołowy, Morak-Młodawska, Study of the lipophilicity and ADMET parameters of new anticancer diquinothiazines with pharmacophore substituents, Pharmaceuticals,
doi:10.3390/ph17060725Kumar, Bhasker, Nikhil, Srinivas, Role of phenylpropanoids and flavonoids in plant defense mechanism, International Journal of Environment and Climate Change,
doi:10.9734/ijecc/2023/v13i92534Li, Fang, Li, Pan, Qin et al., CT image visual quantitative evaluation and clinical classification of coronavirus disease (COVID-19), European Radiology,
doi:10.1007/s00330-020-06817-6Li, Yang, Liu, -F, Ma et al., Overview of therapeutic drug research for COVID-19 in China, Acta Pharmacologica Sinica,
doi:10.1038/s41401-020-0438-yLiu, Yang, Gan, Chen, Xiao et al., CB-Dock2: Improved protein-ligand blind docking by integrating cavity detection, docking and homologous template fitting, Nucleic Acids Research,
doi:10.1093/nar/gkac394Mahesh, Leno, Hacholli, Repurposing of isolated phytochemicals for its antiviral activity against SARS covid-19 through in-silico evaluation, Bull. Env. Pharmacol. Life Sci
Mohammed, El Souda, Taie, Moharam, Shaker, Antioxidant, antimicrobial activities of flavonoids glycoside from Leucaena leucocephala leaves, Journal of Applied Pharmaceutical Science,
doi:10.7324/JAPS.2015.50623Mrityunjaya, Pavithra, Neelam, Janhavi, Halami et al., Immune-boosting, antioxidant and anti-inflammatory food supplements targeting pathogenesis of COVID-19, Frontiers in Immunology,
doi:10.3389/fimmu.2020.570122Mumtaz, Shoaib, Zaib, Shah, Bhatti et al., Synthesis, molecular modelling and biological evaluation of tetrasubstituted thiazoles towards cholinesterase enzymes and cytotoxicity studies, Bioorganic Chemistry,
doi:10.1016/j.bioorg.2018.02.024Napolitano, Lankin, Chen, Pauli, Complete 1H NMR spectral analysis of ten chemical markers of Ginkgo biloba, Magnetic Resonance in Chemistry,
doi:10.1002/mrc.3829Nedyalkova, Simeonov, Partitioning pattern of natural products based on molecular properties descriptors representing drug-likeness, Symmetry,
doi:10.3390/sym13040546Nisar, Gondal, Cheema, Yousaf, Nadeem, New azolederived hemiaminal ethers as promising acetylcholinesterase inhibitors: Synthesis, X-ray structures, in vitro and in silico studies, Journal of Biomolecular Structure and Dynamics,
doi:10.1080/07391102.2023.2190805Osw, Hs Hussain, Isolation of kaempferol 3-O-rutinoside from Kurdish plant Anchusa Italica Retz. and bioactivity of some extracts, Eurasian Journal of Science & Engineering,
doi:10.23918/eajse.v6i2p141Pettersen, Goddard, Huang, Couch, Greenblatt et al., UCSF Chimera-a visualization system for exploratory research and analysis, Journal of Computational Chemistry,
doi:10.1002/jcc.20084Pires, Blundell, Ascher, pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures, Journal of Medicinal Chemistry,
doi:10.1021/acs.jmedchem.5b00104Qawoogha, Shahiwala, Identification of potential anticancer phytochemicals against colorectal cancer by structure-based docking studies, Journal of Receptors and Signal Transduction,
doi:10.1080/10799893.2020.1715431Rahman, Tabrez, Ali, Alqahtani, Ahmed et al., Molecular docking analysis of rutin reveals possible inhibition of SARS-CoV-2 vital proteins, Journal of traditional and complementary medicine,
doi:10.1016/j.jtcme.2021.01.006Ramaroson, Koutouan, Helesbeux, Le Clerc, Hamama et al., Role of phenylpropanoids and flavonoids in plant resistance to pests and diseases, Molecules,
doi:10.3390/molecules27238371Ravi, Kannabiran, A handbook on protein-ligand docking tool: AutoDock 4, Innovare Journal of Medical Sciences
Rha, Jeong, Park, Lee, Jung et al., Antioxidative, anti-inflammatory, and anticancer effects of purified flavonol glycosides and aglycones in green tea, Antioxidants,
doi:10.3390/antiox8080278S ¸erban, Pop, Horvath, Bota, The isolation and identification of rutin from pharmaceutical products,
doi:10.5555/20173102478Sangeetha, Umamaheswari, Reddy, Kalkura, Flavonoids: Therapeutic potential of natural pharmacological agents, International Journal of Pharmaceutical Sciences and Research,
doi:10.13040/IJPSR.0975-8232.7Senthamilselvi, Kesavan, Sulochana, An anti-inflammatory and anti-microbial flavone glycoside from flowers of Cleome viscosa, Organic and medicinal chemistry letters,
doi:10.1186/2191-2858-2-19Shahbaz, Iqbal, Abbasi, Akhtar, Fatima et al., Research article antioxidant, anticancer, and PXR-dependent CYP3A4 attributes of schweinfurthia papilionacea (burm. F.) boiss. Tricholepis glaberrima DC. and Viola stocksii Boiss,
doi:10.1155/2022/9366223Singh, Gupta, Pandey, Exogenous application of rutin and gallic acid regulate antioxidants and alleviate reactive oxygen generation in Oryza sativa L, Physiology and Molecular Biology of Plants,
doi:10.1007/s12298-017-0430-2Soberón, Sgariglia, Sampietro, Quiroga, Vattuone, Free radical scavenging activities and inhibition of inflammatory enzymes of phenolics isolated from Tripodanthus acutifolius, Journal of Ethnopharmacology,
doi:10.1016/j.jep.2010.05.015Su, Li, Zhu, Evaluation of the in vivo anti-inflammatory activity of a flavone glycoside from Cancrinia discoidea (Ledeb.) Poljak, EXCLI journal
Suryawanshi, Jayannache, Patil, Ms, Sg, Molecular docking studies on screening and assessment of selected bioflavonoids as potential inhibitors of COVID-19 main protease, Asian J Pharm Clin Res,
doi:10.22159/ajpcr.2020.v13i9.38485Walther, Schmidtke, Anti-rhinovirus and anti-influenza virus activities of mucoactive secretolytic agents and plant extracts-a comparative in vitro study,
doi:10.21203/rs.2.23461/v1Wang, Lai, Yan, Jin, Yi et al., COVID-19 clinical trials registered worldwide for drug intervention: An overview and characteristic analysis, Drug Design, Development and Therapy,
doi:10.2147/DDDT.S281700Xiao, Dietary flavonoid aglycones and their glycosides: Which show better biological significance?, Critical Reviews in Food Science and Nutrition,
doi:10.1080/10408398.2015.1032400Xie, Deng, Zhang, Dong, Wang et al., Comparison of flavonoid O-glycoside, C-glycoside and their aglycones on antioxidant capacity and metabolism during in vitro digestion and in vivo, Foods,
doi:10.3390/foods11060882Xie, Veitch, Houghton, Simmonds, Flavone C-glycosides from Viola yedoensis M akino, Chemical and Pharmaceutical Bulletin,
doi:10.1248/cpb.51.1204Xu, Xu, Zhang, Yang, Yin et al., Porcine epidemic diarrhea virus infections induce apoptosis in Vero cells via a reactive oxygen species (ROS)/p53, but not p38 MAPK and SAPK/JNK signalling pathways, Veterinary Microbiology,
doi:10.1016/j.vetmic.2019.03.028Xu, Zhu, Wang, Lin, Sun et al., Phenolic glycosides and flavonoids with antioxidant and anticancer activities from Desmodium caudatum, Natural Product Research,
doi:10.1080/14786419.2020.1739044Yuan, Chan, Hu, Using PyMOL as a platform for computational drug design, Wiley Interdisciplinary Reviews: Computational Molecular Science,
doi:10.1002/wcms.1298Zhan, Tian, Zhang, Xing, Song et al., Structural study of SARS-CoV-2 antibodies identifies a broadspectrum antibody that neutralizes the omicron variant by disassembling the spike trimer, Journal of Virology,
doi:10.1128/jvi.00480-22Zhao, Ding, Chu, Zhang, Wang et al., Plant immune inducer ZNC promotes rutin accumulation and enhances resistance to Botrytis cinerea in tomato, Stress Biology,
doi:10.1007/s44154-023-00106-0Zoete, Cuendet, Grosdidier, Michielin, SwissParam: A fast force field generation tool for small organic molecules, Journal of Computational Chemistry,
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'DOI': '10.1016/j.ijbiomac.2022.09.204',
'article-title': 'Agathisflavone, a natural biflavonoid that inhibits SARS-CoV-2 '
'replication by targeting its proteases',
'volume': '222',
'author': 'Chaves',
'year': '2022',
'journal-title': 'International Journal of Biological Macromolecules'},
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'first-page': '21',
'DOI': '10.3390/ph15010021',
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'variants replication in vitro and in vivo',
'volume': '15',
'author': 'Chaves',
'year': '2021',
'journal-title': 'Pharmaceuticals'},
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'article-title': 'New benzotriazole-derived α-substituted hemiaminal ethers with enhanced '
'cholinesterase inhibition activity: Synthesis, structural, and '
'biological evaluations',
'volume': '27',
'author': 'Cheema',
'year': '2023',
'journal-title': 'Journal of Saudi Chemical Society'},
{ 'year': '2012',
'series-title': 'admetSAR: a comprehensive source and free tool for assessment of '
'chemical ADMET properties',
'author': 'Cheng',
'key': '10.1016/j.fbio.2024.105095_bib15'},
{'author': 'Cherrak', 'key': '10.1016/j.fbio.2024.105095_bib16'},
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'first-page': '1304',
'DOI': '10.3390/nu9121304',
'article-title': 'Elucidating the skin delivery of aglycone and glycoside flavonoids: How '
'the structures affect cutaneous absorption',
'volume': '9',
'author': 'Chuang',
'year': '2017',
'journal-title': 'Nutrients'},
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'first-page': '339',
'article-title': 'Coronavirus COV-19/SARS-CoV-2 affects women less than men: Clinical '
'response to viral infection',
'volume': '34',
'author': 'Conti',
'year': '2020',
'journal-title': 'Journal of Biological Regulators & Homeostatic Agents'},
{ 'volume': '115',
'year': '2020',
'author': 'da Silva',
'key': '10.1016/j.fbio.2024.105095_bib19'},
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'doi-asserted-by': 'crossref',
'DOI': '10.1038/srep42717',
'article-title': 'SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness '
'and medicinal chemistry friendliness of small molecules',
'volume': '7',
'author': 'Daina',
'year': '2017',
'journal-title': 'Scientific Reports'},
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'first-page': '82',
'article-title': 'Pymol: An open-source molecular graphics tool. CCP4 Newsl',
'volume': '40',
'author': 'DeLano',
'year': '2002',
'journal-title': 'Protein Crystallogr'},
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'doi-asserted-by': 'crossref',
'first-page': '1808',
'DOI': '10.1002/jmv.27601',
'article-title': 'Emergence of Omicron third lineage BA. 3 and its importance',
'volume': '94',
'author': 'Desingu',
'year': '2022',
'journal-title': 'Journal of Medical Virology'},
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'doi-asserted-by': 'crossref',
'first-page': '33',
'DOI': '10.1016/j.bbrc.2013.10.164',
'article-title': 'Regulation of ROS in transmissible gastroenteritis virus-activated '
'apoptotic signaling',
'volume': '442',
'author': 'Ding',
'year': '2013',
'journal-title': 'Biochemical and biophysical research communications'},
{ 'key': '10.1016/j.fbio.2024.105095_bib24',
'doi-asserted-by': 'crossref',
'DOI': '10.1155/2020/3173281',
'article-title': 'Natural antioxidants: A review of studies on human and animal '
'coronavirus',
'author': 'Diniz',
'year': '2020',
'journal-title': 'Oxidative Medicine and Cellular Longevity'},
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'doi-asserted-by': 'crossref',
'first-page': 'W53',
'DOI': '10.1093/nar/gku401',
'article-title': 'ProTox: A web server for the in silico prediction of rodent oral '
'toxicity',
'volume': '42',
'author': 'Drwal',
'year': '2014',
'journal-title': 'Nucleic Acids Research'},
{'author': 'El-Hadary', 'key': '10.1016/j.fbio.2024.105095_bib26'},
{ 'key': '10.1016/j.fbio.2024.105095_bib27',
'doi-asserted-by': 'crossref',
'DOI': '10.18502/jfqhc.10.1.11988',
'article-title': 'Comparative effects of hibiscus leaves and potato peel extracts on '
'characteristics of fermented orange juice',
'author': 'El-Hadary',
'year': '2023',
'journal-title': 'Journal of food quality and hazards control'},
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'doi-asserted-by': 'crossref',
'first-page': '1',
'DOI': '10.1186/s12575-020-00128-2',
'article-title': 'A comprehensive review of COVID-19 characteristics',
'volume': '22',
'author': 'Esakandari',
'year': '2020',
'journal-title': 'Biological Procedures Online'},
{'author': 'Fathi', 'key': '10.1016/j.fbio.2024.105095_bib29'},
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'first-page': '762',
'DOI': '10.3390/molecules25030762',
'article-title': 'Therapeutic potential of flavonoids in pain and inflammation: '
'Mechanisms of action, pre-clinical and clinical data, and '
'pharmaceutical development',
'volume': '25',
'author': 'Ferraz',
'year': '2020',
'journal-title': 'Molecules'},
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'doi-asserted-by': 'crossref',
'DOI': '10.3389/fnins.2021.729757',
'article-title': 'Oxidative stress and cognitive decline: The neuroprotective role of '
'natural antioxidants',
'volume': '15',
'author': 'Franzoni',
'year': '2021',
'journal-title': 'Frontiers in Neuroscience'},
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'doi-asserted-by': 'crossref',
'first-page': '2099',
'DOI': '10.1021/acsinfecdis.0c00168',
'article-title': 'Characterization and noncovalent inhibition of the deubiquitinase and '
'deISGylase activity of SARS-CoV-2 papain-like protease',
'volume': '6',
'author': 'Freitas',
'year': '2020',
'journal-title': 'ACS Infectious Diseases'},
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'doi-asserted-by': 'crossref',
'first-page': '2994',
'DOI': '10.3390/molecules25132994',
'article-title': 'Anti-inflammatory principles from tamarix aphylla L.: A bioassay-guided '
'fractionation study',
'volume': '25',
'author': 'Gadallah',
'year': '2020',
'journal-title': 'Molecules'},
{ 'key': '10.1016/j.fbio.2024.105095_bib34',
'first-page': '28',
'article-title': 'In silico interaction of hesperidin with some immunomodulatory targets: '
'A docking analysis',
'volume': '56',
'author': 'Ganeshpurkar',
'year': '2019',
'journal-title': 'Indian Journal of Biochemistry & Biophysics'},
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'doi-asserted-by': 'crossref',
'first-page': '546',
'DOI': '10.3390/ph14060546',
'article-title': 'Therapeutic potential of glycosyl flavonoids as anti-coronaviral agents',
'volume': '14',
'author': 'Godinho',
'year': '2021',
'journal-title': 'Pharmaceuticals'},
{ 'key': '10.1016/j.fbio.2024.105095_bib36',
'doi-asserted-by': 'crossref',
'DOI': '10.1111/sji.13106',
'article-title': 'Immunomodulatory potential of flavonoids for the treatment of '
'autoimmune diseases and tumour',
'volume': '95',
'author': 'Han',
'year': '2022',
'journal-title': 'Scandinavian Journal of Immunology'},
{ 'year': '2013',
'series-title': 'The flavonoids: Advances in research',
'author': 'Harborne',
'key': '10.1016/j.fbio.2024.105095_bib37'},
{ 'key': '10.1016/j.fbio.2024.105095_bib38',
'doi-asserted-by': 'crossref',
'first-page': '1391',
'DOI': '10.1016/0031-9422(92)80298-S',
'article-title': 'Complex flavonol glycosides from the leaves of Ginkgo biloba',
'volume': '31',
'author': 'Hasler',
'year': '1992',
'journal-title': 'Phytochemistry'},
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'doi-asserted-by': 'crossref',
'first-page': '492',
'DOI': '10.1084/jem.156.2.492',
'article-title': 'Chemiluminescence response of human natural killer cells. I. The '
'relationship between target cell binding, chemiluminescence, and '
'cytolysis',
'volume': '156',
'author': 'Helfand',
'year': '1982',
'journal-title': 'The Journal of experimental medicine'},
{ 'article-title': 'Flavonoids: Potential therapeutic agents by their antioxidant capacity',
'year': '2019',
'series-title': 'Bioactive compounds',
'author': 'Hernández-Rodríguez',
'key': '10.1016/j.fbio.2024.105095_bib40'},
{ 'key': '10.1016/j.fbio.2024.105095_bib41',
'doi-asserted-by': 'crossref',
'first-page': '9196',
'DOI': '10.1016/j.arabjc.2020.11.004',
'article-title': 'Anti-inflammatory, analgesic and molecular docking studies of '
'Lanostanoic acid 3-O-α-D-glycopyranoside isolated from Helichrysum '
'stoechas',
'volume': '13',
'author': 'Hussain',
'year': '2020',
'journal-title': 'Arabian Journal of Chemistry'},
{ 'key': '10.1016/j.fbio.2024.105095_bib42',
'doi-asserted-by': 'crossref',
'DOI': '10.1016/j.jmgm.2021.107904',
'article-title': 'Rutin and flavone analogs as prospective SARS-CoV-2 main protease '
'inhibitors: In silico drug discovery study',
'volume': '105',
'author': 'Ibrahim',
'year': '2021',
'journal-title': 'Journal of Molecular Graphics and Modelling'},
{ 'key': '10.1016/j.fbio.2024.105095_bib43',
'doi-asserted-by': 'crossref',
'first-page': '123',
'DOI': '10.1016/j.bse.2013.08.004',
'article-title': 'Flavones and anthocyanins from the leaves and flowers of Japanese Ajuga '
'species (Lamiaceae)',
'volume': '51',
'author': 'Inomata',
'year': '2013',
'journal-title': 'Biochemical Systematics and Ecology'},
{ 'key': '10.1016/j.fbio.2024.105095_bib44',
'first-page': '171',
'article-title': "Lipinski's rule of five, famous extensions and famous exceptions",
'volume': '3',
'author': 'Ivanović',
'year': '2020',
'journal-title': 'Popular Scientific Article'},
{'author': 'Jejurikar', 'key': '10.1016/j.fbio.2024.105095_bib45'},
{ 'key': '10.1016/j.fbio.2024.105095_bib46',
'doi-asserted-by': 'crossref',
'first-page': '289',
'DOI': '10.1038/s41586-020-2223-y',
'article-title': 'Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors',
'volume': '582',
'author': 'Jin',
'year': '2020',
'journal-title': 'Nature'},
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'doi-asserted-by': 'crossref',
'first-page': '692',
'DOI': '10.1080/14786419.2018.1493588',
'article-title': 'Flavonoids: Biological activities and therapeutic potential',
'volume': '34',
'author': 'Jucá',
'year': '2020',
'journal-title': 'Natural Product Research'},
{ 'key': '10.1016/j.fbio.2024.105095_bib48',
'article-title': 'Potential inhibitor of COVID-19 main protease (Mpro) from several '
'medicinal plant compounds by molecular docking study',
'volume': '2020',
'author': 'Khaerunnisa',
'year': '2020',
'journal-title': 'Preprints'},
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'doi-asserted-by': 'crossref',
'DOI': '10.1016/j.genrep.2020.100682',
'article-title': 'Genomic characterization of a novel SARS-CoV-2',
'volume': '19',
'author': 'Khailany',
'year': '2020',
'journal-title': 'Gene reports'},
{ 'key': '10.1016/j.fbio.2024.105095_bib50',
'doi-asserted-by': 'crossref',
'DOI': '10.15252/embj.2020106275',
'article-title': 'Mechanism and inhibition of the papain‐like protease, PLpro, of '
'SARS‐CoV‐2',
'volume': '39',
'author': 'Klemm',
'year': '2020',
'journal-title': 'The EMBO journal'},
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'doi-asserted-by': 'crossref',
'first-page': '725',
'DOI': '10.3390/ph17060725',
'article-title': 'Study of the lipophilicity and ADMET parameters of new anticancer '
'diquinothiazines with pharmacophore substituents',
'volume': '17',
'author': 'Klimoszek',
'year': '2024',
'journal-title': 'Pharmaceuticals'},
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'doi-asserted-by': 'crossref',
'first-page': '2951',
'DOI': '10.9734/ijecc/2023/v13i92534',
'article-title': 'Role of phenylpropanoids and flavonoids in plant defense mechanism',
'volume': '13',
'author': 'Kumar',
'year': '2023',
'journal-title': 'International Journal of Environment and Climate Change'},
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'doi-asserted-by': 'crossref',
'first-page': '4407',
'DOI': '10.1007/s00330-020-06817-6',
'article-title': 'CT image visual quantitative evaluation and clinical classification of '
'coronavirus disease (COVID-19)',
'volume': '30',
'author': 'Li',
'year': '2020',
'journal-title': 'European Radiology'},
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'doi-asserted-by': 'crossref',
'first-page': '1133',
'DOI': '10.1038/s41401-020-0438-y',
'article-title': 'Overview of therapeutic drug research for COVID-19 in China',
'volume': '41',
'author': 'Li',
'year': '2020',
'journal-title': 'Acta Pharmacologica Sinica'},
{ 'key': '10.1016/j.fbio.2024.105095_bib55',
'doi-asserted-by': 'crossref',
'first-page': 'W159',
'DOI': '10.1093/nar/gkac394',
'article-title': 'CB-Dock2: Improved protein–ligand blind docking by integrating cavity '
'detection, docking and homologous template fitting',
'volume': '50',
'author': 'Liu',
'year': '2022',
'journal-title': 'Nucleic Acids Research'},
{ 'key': '10.1016/j.fbio.2024.105095_bib56',
'doi-asserted-by': 'crossref',
'first-page': '381',
'DOI': '10.1146/annurev-biochem-052521-115653',
'article-title': 'The life of SARS-CoV-2 inside cells: Replication–transcription complex '
'assembly and function',
'volume': '91',
'author': 'Lou',
'year': '2022',
'journal-title': 'Annual Review of Biochemistry'},
{ 'key': '10.1016/j.fbio.2024.105095_bib57',
'first-page': '227',
'article-title': 'Repurposing of isolated phytochemicals for its antiviral activity '
'against SARS covid-19 through in-silico evaluation',
'volume': '12',
'author': 'Mahesh',
'year': '2023',
'journal-title': 'Bull. Env. Pharmacol. Life Sci'},
{ 'key': '10.1016/j.fbio.2024.105095_bib58',
'doi-asserted-by': 'crossref',
'DOI': '10.1126/science.123.3194.464.a',
'article-title': 'Artemia salina as a test organism for bioassay',
'volume': '123',
'author': 'Michael',
'year': '1956',
'journal-title': 'Science'},
{ 'key': '10.1016/j.fbio.2024.105095_bib59',
'doi-asserted-by': 'crossref',
'first-page': '138',
'DOI': '10.7324/JAPS.2015.50623',
'article-title': 'Antioxidant, antimicrobial activities of flavonoids glycoside from '
'Leucaena leucocephala leaves',
'volume': '5',
'author': 'Mohammed',
'year': '2015',
'journal-title': 'Journal of Applied Pharmaceutical Science'},
{ 'key': '10.1016/j.fbio.2024.105095_bib60',
'article-title': 'Immune-boosting, antioxidant and anti-inflammatory food supplements '
'targeting pathogenesis of COVID-19',
'volume': '2337',
'author': 'Mrityunjaya',
'year': '2020',
'journal-title': 'Frontiers in Immunology'},
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'doi-asserted-by': 'crossref',
'first-page': '302',
'DOI': '10.1002/med.10041',
'article-title': 'Selection criteria for drug‐like compounds',
'volume': '23',
'author': 'Muegge',
'year': '2003',
'journal-title': 'Medicinal Research Reviews'},
{ 'key': '10.1016/j.fbio.2024.105095_bib62',
'doi-asserted-by': 'crossref',
'first-page': '141',
'DOI': '10.1016/j.bioorg.2018.02.024',
'article-title': 'Synthesis, molecular modelling and biological evaluation of '
'tetrasubstituted thiazoles towards cholinesterase enzymes and '
'cytotoxicity studies',
'volume': '78',
'author': 'Mumtaz',
'year': '2018',
'journal-title': 'Bioorganic Chemistry'},
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'doi-asserted-by': 'crossref',
'first-page': '569',
'DOI': '10.1002/mrc.3829',
'article-title': 'Complete 1H NMR spectral analysis of ten chemical markers of Ginkgo '
'biloba',
'volume': '50',
'author': 'Napolitano',
'year': '2012',
'journal-title': 'Magnetic Resonance in Chemistry'},
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'doi-asserted-by': 'crossref',
'first-page': '546',
'DOI': '10.3390/sym13040546',
'article-title': 'Partitioning pattern of natural products based on molecular properties '
'descriptors representing drug-likeness',
'volume': '13',
'author': 'Nedyalkova',
'year': '2021',
'journal-title': 'Symmetry'},
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'first-page': '15535',
'DOI': '10.1080/07391102.2023.2190805',
'article-title': 'New azole-derived hemiaminal ethers as promising acetylcholinesterase '
'inhibitors: Synthesis, X-ray structures, in vitro and in silico studies',
'volume': '41',
'author': 'Nisar',
'year': '2023',
'journal-title': 'Journal of Biomolecular Structure and Dynamics'},
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'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': 'Journal of Computational Chemistry'},
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'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': 'Pires',
'year': '2015',
'journal-title': 'Journal of Medicinal Chemistry'},
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'doi-asserted-by': 'crossref',
'first-page': '508',
'DOI': '10.1016/j.chom.2021.02.020',
'article-title': "The variant gambit: COVID-19's next move",
'volume': '29',
'author': 'Plante',
'year': '2021',
'journal-title': 'Cell host & microbe'},
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'doi-asserted-by': 'crossref',
'first-page': '122',
'DOI': '10.14499/indonesianjcanchemoprev10iss3pp122-130',
'article-title': 'Molecular docking study of akar kuning (arcangelisia flava) secondary '
'metabolites as Src inhibitor',
'volume': '10',
'author': 'Pratama',
'year': '2019',
'journal-title': 'Indonesian Journal of Cancer Chemoprevention'},
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'doi-asserted-by': 'crossref',
'first-page': '67',
'DOI': '10.1080/10799893.2020.1715431',
'article-title': 'Identification of potential anticancer phytochemicals against '
'colorectal cancer by structure-based docking studies',
'volume': '40',
'author': 'Qawoogha',
'year': '2020',
'journal-title': 'Journal of Receptors and Signal Transduction'},
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'first-page': '173',
'DOI': '10.1016/j.jtcme.2021.01.006',
'article-title': 'Molecular docking analysis of rutin reveals possible inhibition of '
'SARS-CoV-2 vital proteins',
'volume': '11',
'author': 'Rahman',
'year': '2021',
'journal-title': 'Journal of traditional and complementary medicine'},
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'first-page': '8371',
'DOI': '10.3390/molecules27238371',
'article-title': 'Role of phenylpropanoids and flavonoids in plant resistance to pests '
'and diseases',
'volume': '27',
'author': 'Ramaroson',
'year': '2022',
'journal-title': 'Molecules'},
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'first-page': '28',
'article-title': 'A handbook on protein-ligand docking tool: AutoDock 4',
'author': 'Ravi',
'year': '2016',
'journal-title': 'Innovare Journal of Medical Sciences'},
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'doi-asserted-by': 'crossref',
'first-page': '278',
'DOI': '10.3390/antiox8080278',
'article-title': 'Antioxidative, anti-inflammatory, and anticancer effects of purified '
'flavonol glycosides and aglycones in green tea',
'volume': '8',
'author': 'Rha',
'year': '2019',
'journal-title': 'Antioxidants'},
{'author': 'Şerban', 'key': '10.1016/j.fbio.2024.105095_bib75'},
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'first-page': '141',
'article-title': 'Isolation of kaempferol 3-O-rutinoside from Kurdish plant Anchusa '
'Italica Retz. and bioactivity of some extracts',
'volume': '6',
'author': 'S Osw',
'year': '2020',
'journal-title': 'Eurasian Journal of Science & Engineering'},
{ 'key': '10.1016/j.fbio.2024.105095_bib77',
'first-page': '3924',
'article-title': 'Flavonoids: Therapeutic potential of natural pharmacological agents',
'volume': '7',
'author': 'Sangeetha',
'year': '2016',
'journal-title': 'International Journal of Pharmaceutical Sciences and Research'},
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'first-page': '1',
'DOI': '10.1186/2191-2858-2-19',
'article-title': 'An anti-inflammatory and anti-microbial flavone glycoside from flowers '
'of Cleome viscosa',
'volume': '2',
'author': 'Senthamilselvi',
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