{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T22:21:16Z","timestamp":1783635676647,"version":"3.55.0"},"reference-count":123,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T00:00:00Z","timestamp":1664236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The recent coronavirus disease (COVID-19) outbreak in Wuhan, China, has led to millions of infections and the death of approximately one million people. No targeted therapeutics are currently available, and only a few efficient treatment options are accessible. Many researchers are investigating active compounds from natural plant sources that may inhibit COVID-19 proliferation. Flavonoids are generally present in our diet, as well as traditional medicines and are effective against various diseases. Thus, here, we reviewed the potential of flavonoids against crucial proteins involved in the coronavirus infectious cycle. The fundamentals of coronaviruses, the structures of SARS-CoV-2, and the mechanism of its entry into the host\u2019s body have also been discussed. In silico studies have been successfully employed to study the interaction of flavonoids against COVID-19 Mpro, spike protein PLpro, and other interactive sites for its possible inhibition. Recent studies showed that many flavonoids such as hesperidin, amentoflavone, rutin, diosmin, apiin, and many other flavonoids have a higher affinity with Mpro and lower binding energy than currently used drugs such as hydroxylchloroquine, nelfinavir, ritonavir, and lopinavir. Thus, these compounds can be developed as specific therapeutic agents against COVID-19, but need further in vitro and in vivo studies to validate these compounds and pave the way for drug discovery.<\/jats:p>","DOI":"10.3390\/molecules27196374","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T03:30:37Z","timestamp":1664335837000},"page":"6374","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["In Silico Evaluation of Natural Flavonoids as a Potential Inhibitor of Coronavirus Disease"],"prefix":"10.3390","volume":"27","author":[{"given":"Piyush","family":"Kashyap","sequence":"first","affiliation":[{"name":"Department of Food Technology and Nutrition, School of Agriculture, Lovely Professional University, Phagwara 144401, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6052-6819","authenticated-orcid":false,"given":"Mamta","family":"Thakur","sequence":"additional","affiliation":[{"name":"Department of Food Technology, School of Sciences, ITM University, Gwalior 474001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidhi","family":"Singh","sequence":"additional","affiliation":[{"name":"Centre of Bioinformatics, University of Allahabad, Prayraj 211002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deep","family":"Shikha","sequence":"additional","affiliation":[{"name":"Department of Food Technology, Bhai Gurdas Institute of Engineering and Technology, Sangrur 148001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0655-9561","authenticated-orcid":false,"given":"Shiv","family":"Kumar","sequence":"additional","affiliation":[{"name":"MMICT & BM (HM), Maharishi Markandeshwar Deemed to be University, Mullana, Ambala 133207, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poonam","family":"Baniwal","sequence":"additional","affiliation":[{"name":"Department of Quality Control, Food Corporation of India, New Delhi 110001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6638-9926","authenticated-orcid":false,"given":"Yogender Singh","family":"Yadav","sequence":"additional","affiliation":[{"name":"Department of Dairy Engineering, College of Dairy Science and Technology, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar 125004, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6493-5217","authenticated-orcid":false,"given":"Minaxi","family":"Sharma","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimieverte et Produits Biobas\u00e9s, D\u00e9partement AgroBioscience et Chimie, Haute Ecole Provinciale du Hainaut-Condorcet, 11, 7800 ATH Rue de la Sucrerie, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6174-0024","authenticated-orcid":false,"given":"Kandi","family":"Sridhar","sequence":"additional","affiliation":[{"name":"UMR1253, Science et Technologie du Lait et de l\u2019\u0153uf, INRAE, L\u2019InstitutAgro, Rennes-Angers, 65 Rue de Saint Brieuc, F-35042 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4301-7614","authenticated-orcid":false,"given":"Baskaran Stephen","family":"Inbaraj","sequence":"additional","affiliation":[{"name":"Department of Food Science, Fu Jen Catholic University, New Taipei City 242 05, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,27]]},"reference":[{"key":"ref_1","unstructured":"WHO (2022, April 14). Coronavirus Disease (COVID-19), Available online: https:\/\/covid19.who.int\/."},{"key":"ref_2","unstructured":"WHO (2020, June 17). WHO Welcomes Preliminary Results about Dexamethasone Use in Treating Critically Ill COVID-19 Patients. World Health Organization, Geneva, Available online: https:\/\/www.who.int\/news-room\/detail\/16-06-2020-who-welcomes-preliminary-results-about-dexamethasone-use-in-treating-critically-ill-covid-19-patients."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/ijp.IJP_119_20","article-title":"Therapeutic options for the treatment of 2019-novel coronavirus: An evidence-based approach","volume":"52","author":"Sarma","year":"2020","journal-title":"Indian J. Pharmacol."},{"key":"ref_4","first-page":"3422","article-title":"COVID-19 Emerging protective measures","volume":"24","author":"Balachandar","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_5","first-page":"845","article-title":"The performance of current methods in ligand\u2013protein docking","volume":"83","author":"McConkey","year":"2002","journal-title":"Curr. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"509","DOI":"10.2174\/1381612013397861","article-title":"Virtual screening an effective tool for lead structure discovery","volume":"7","author":"Langer","year":"2001","journal-title":"Curr. Pharm. Des."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1038\/nrd941","article-title":"Integration of virtual and high-throughput screening","volume":"1","author":"Bajorath","year":"2002","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1126\/science.1096361","article-title":"The many roles of computation in drug discovery","volume":"303","author":"Jorgensen","year":"2004","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1038\/nrd1549","article-title":"Docking and scoring in virtual screening for drug discovery: Methods and applications","volume":"3","author":"Kitchen","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Xu, Z., Peng, C., Shi, Y., Zhu, Z., Mu, K., Wang, X., and Zhu, W. (2020). Nelfinavir was predicted to be a potential inhibitor of 2019-nCov main protease by an integrative approach combining homology modelling, molecular docking and binding free energy calculation. BioRxiv, 1\u201320.","DOI":"10.1101\/2020.01.27.921627"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.semcancer.2017.05.005","article-title":"Antioxidant polyphenols in cancer treatment: Friend, foe or foil?","volume":"46","author":"Russo","year":"2017","journal-title":"Sem. Cancer Biolog."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ejmech.2017.09.001","article-title":"Anti-inflammatory effects of flavonoids in neurodegenerative disorders","volume":"153","author":"Spagnuolo","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_13","first-page":"95","article-title":"HIV protease inhibitors: A review of molecular selectivity and toxicity","volume":"7","author":"Lv","year":"2015","journal-title":"HIV\/AIDS"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"69","DOI":"10.5582\/bst.2020.01020","article-title":"Drug treatment options for the 2019-new coronavirus (2019-nCoV)","volume":"14","author":"Lu","year":"2020","journal-title":"Biosci. Trends"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1080\/14756366.2019.1690480","article-title":"Inhibition of SARS-CoV 3CL protease by flavonoids","volume":"35","author":"Jo","year":"2020","journal-title":"J. Enzyme.Inhib. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2478\/bile-2020-0002","article-title":"Meta-analysis of flavonoids with antiviral potential against coronavirus","volume":"57","author":"Sawikowska","year":"2020","journal-title":"Biom. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.antiviral.2005.07.002","article-title":"Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds","volume":"68","author":"Lin","year":"2005","journal-title":"Antivir. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.jep.2008.03.018","article-title":"Immunomodulatory and anti-SARS activities of Houttuyniacordata","volume":"118","author":"Lau","year":"2008","journal-title":"J. Ethnopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7940","DOI":"10.1016\/j.bmc.2010.09.035","article-title":"Biflavonoids from Torreyan ucifera displaying SARS-CoV 3CLpro inhibition","volume":"18","author":"Ryu","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"129","DOI":"10.12688\/f1000research.22457.2","article-title":"Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL pro) structure: Virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates","volume":"9","author":"Chen","year":"2020","journal-title":"F1000Research"},{"key":"ref_22","first-page":"1","article-title":"Potential inhibitor of COVID-19 main protease (Mpro) from several medicinal plant compounds by molecular docking study","volume":"20944","author":"Khaerunnisa","year":"2020","journal-title":"Preprints"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Peterson, L. (2022, March 05). COVID-19 and Flavonoids: In silico Molecular Dynamics Docking to the Active Catalytic Site of SARS-CoV and SARS-CoV-2 Main Protease. Available online: https:\/\/papers.ssrn.com\/sol3\/papers.cfm?abstract_id=3599426.","DOI":"10.51483\/AFJPS.2.1.2022.23-42"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Adem, S., Eyupoglu, V., Sarfraz, I., Rasul, A., and Ali, M. (2020). Identification of potent COVID-19 main protease (Mpro) inhibitors from natural polyphenols: An in silico strategy unveils a hope against corona. Preprints, 2020030333.","DOI":"10.20944\/preprints202003.0333.v1"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jpha.2021.09.009","article-title":"Antiviral, immunomodulatory, and anticoagulant effects of quercetin and its derivatives: Potential role in prevention and management of COVID-19","volume":"12","author":"Manjunath","year":"2021","journal-title":"J. Pharm. Anal."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1002\/ptr.6998","article-title":"In silico and in vitro evaluation of kaempferol as a potential inhibitor of the SARS-CoV-2 main protease (3CLpro)","volume":"35","author":"Khan","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Nguyen, T.T.H., Jung, J.H., Kim, M.K., Lim, S., Choi, J.M., Chung, B., Kim, D.W., and Kim, D. (2021). The inhibitory effects of plant derivate polyphenols on the main protease of SARS coronavirus 2 and their structure\u2013activity relationship. Molecules, 26.","DOI":"10.3390\/molecules26071924"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Cherrak, S.A., Merzouk, H., and Mokhtari-Soulimane, N. (2020). Potential bioactive glycosylated flavonoids as SARS-CoV-2 main protease inhibitors: A molecular docking and simulation studies. PLoS ONE, 15.","DOI":"10.31219\/osf.io\/k4h5f"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"32148","DOI":"10.1039\/D0RA05679K","article-title":"Inhibition of SARS-CoV-2 main protease by phenolic compounds from Manilkarahexandra (Roxb.) Dubard assisted by metabolite profiling and in silico virtual screening","volume":"10","author":"Ibrahim","year":"2020","journal-title":"RSC Adv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4988","DOI":"10.1002\/ptr.7131","article-title":"New perspectives on natural flavonoids on COVID-19-induced lung injuries","volume":"35","author":"Santana","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1080\/14756366.2020.1801672","article-title":"Flavonoids with inhibitory activity against SARS-CoV-2 3CLpro","volume":"35","author":"Jo","year":"2020","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/nrmicro2147","article-title":"Coronaviruses post-SARS: Update on replication and pathogenesis","volume":"7","author":"Perlman","year":"2020","journal-title":"Nat. Rev.Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/s41564-020-0695-z","article-title":"The species severe acute respiratory syndrome related coronavirus: Classifying 2019-nCoV and naming it SARS-CoV-2","volume":"5","author":"Gorbalenya","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/S0140-6736(03)13077-2","article-title":"Coronavirus as a possible cause of severe acute respiratory syndrome","volume":"361","author":"Peiris","year":"2003","journal-title":"Lancet"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1146\/annurev-virology-110615-042301","article-title":"Structure, function, and evolution of coronavirus spike proteins","volume":"3","author":"Li","year":"2016","journal-title":"Ann. Rev. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S0140-6736(20)30251-8","article-title":"Genomic characterization and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding","volume":"395","author":"Lu","year":"2020","journal-title":"Lancet"},{"key":"ref_37","unstructured":"Cascella, M., Rajnik, M., Cuomo, A., Dulebohn, S.C., and Di Napoli, R. (2020). Features, Evaluation and Treatment Coronavirus (COVID-19). Statpearls [Internet], StatPearls Publishing."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical characteristics of coronavirus disease 2019 in China","volume":"2382","author":"Guan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1111\/resp.13196","article-title":"MERS, SARS and other coronaviruses as causes of pneumonia","volume":"23","author":"Yin","year":"2018","journal-title":"Respirology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Gorbalenya, A.E., Baker, S.C., Baric, R., Groot, R.J.D., Drosten, C., Gulyaeva, A.A., Haagmans, B.L., Lauber, C., Leontovich, A.M., and Neuman, B.W. (2020). Severe acute respiratory syndrome-related coronavirus: The species and its viruses\u2014A statement of the Coronavirus Study Group. BioRxiv, 937862.","DOI":"10.1101\/2020.02.07.937862"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.abb3405","article-title":"Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved \u03b1-ketoamide inhibitors","volume":"368","author":"Zhang","year":"2020","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/s41423-020-0400-4","article-title":"Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: Implication for development of RBD protein as a viral attachment inhibitor and vaccine","volume":"17","author":"Tai","year":"2020","journal-title":"Cell Mol. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/S0140-6736(03)14630-2","article-title":"Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People\u2019s Republic of China, in February, 2003","volume":"362","author":"Zhong","year":"2003","journal-title":"Lancet"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41368-020-0075-9","article-title":"Transmission routes of 2019-nCoV and controls in dental practice","volume":"12","author":"Peng","year":"2020","journal-title":"Int. J. Oral Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40779-020-00240-0","article-title":"The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak\u2014An update on the status","volume":"7","author":"Guo","year":"2020","journal-title":"Military Med. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1002\/jmv.25681","article-title":"Emerging coronaviruses: Genome structure, replication, and pathogenesis","volume":"92","author":"Chen","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"56","DOI":"10.4103\/ijp.IJP_115_20","article-title":"Drug targets for corona virus: A systematic review","volume":"52","author":"Prajapat","year":"2020","journal-title":"Indian J. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Sardar, R., Satish, D., Birla, S., and Gupta, D. (2020). Comparative analyses of SAR-CoV2 genomes from different geographical locations and other coronavirus family genomes reveals unique features potentially consequential to host-virus interaction and pathogenesis. BioRxiv, online ahead of print.","DOI":"10.1101\/2020.03.21.001586"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12985-019-1182-0","article-title":"Coronavirus envelope protein: Current knowledge","volume":"16","author":"Schoeman","year":"2019","journal-title":"Virol. J."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Lai, M.M., and Cavanagh, D. (1997). The Molecular Biology of Coronaviruses. Advances in Virus Research, Academic Press.","DOI":"10.1016\/S0065-3527(08)60286-9"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3737","DOI":"10.1128\/JVI.73.5.3737-3743.1999","article-title":"Identification of a coronavirus hemagglutinin-esterase with a substrate specificity different from those of influenza C virus and bovine coronavirus","volume":"73","author":"Klausegger","year":"1999","journal-title":"J. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.3390\/v6082991","article-title":"The coronavirus nucleocapsid is a multifunctional protein","volume":"6","author":"McBride","year":"2014","journal-title":"Viruses"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/nrd.2015.37","article-title":"Coronaviruses\u2014drug discovery and therapeutic options","volume":"15","author":"Zumla","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/S0140-6736(20)30419-0","article-title":"A distinct name is needed for the new coronavirus","volume":"395","author":"Jiang","year":"2020","journal-title":"Lancet"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1002\/jmv.25726","article-title":"Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS-CoV-2","volume":"92","author":"Liu","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"104211","DOI":"10.1016\/j.meegid.2020.104211","article-title":"Novel coronavirus: From discovery to clinical diagnostics","volume":"79","author":"Phan","year":"2020","journal-title":"Infect. Genet. Evol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Zhao, Z., Wang, Y., Zhou, Y., Ma, Y., and Zuo, W. (2020). Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. BioRxiv.","DOI":"10.1101\/2020.01.26.919985"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"6927","DOI":"10.1038\/s41598-021-86380-2","article-title":"In silico investigation of critical binding pattern in SARS-CoV-2 spike protein with angiotensin-converting enzyme 2","volume":"11","author":"Jafary","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1038\/s41467-020-15562-9","article-title":"Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV","volume":"11","author":"Ou","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Grottesi, A., Besker, N., Emerson, A., Manelfi, C., Beccari, A.R., Frigerio, F., Lindahl, E., Cerchia, C., and Talarico, C. (2020). Computational studies of SARS-CoV-2 3CLpro: Insights from MD simulations. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155346"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.arcmed.2020.05.012","article-title":"structural proteins in severe acute respiratory syndrome coronavirus-2","volume":"51","author":"Satarker","year":"2020","journal-title":"Arch. Med. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"eabe5575","DOI":"10.1126\/sciadv.abe5575","article-title":"Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM","volume":"7","author":"Xu","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Gralinski, L.E., and Menachery, V.D. (2020). Return of the Coronavirus: 2019-nCoV. Viruses, 12.","DOI":"10.3390\/v12020135"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/nri.2017.148","article-title":"Passive immunotherapy of viral infections:\u2019 Super-antibodies\u2019 enter the fray","volume":"18","author":"Walker","year":"2018","journal-title":"Nat. Rev.Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.dsx.2020.04.020","article-title":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response","volume":"14","author":"Astuti","year":"2020","journal-title":"Diabetes Metab. Syndr. Clin. Res. Rev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1172\/JCI138003","article-title":"The convalescent sera option for containing COVID-19","volume":"130","author":"Casadevall","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"72","DOI":"10.12688\/f1000research.22211.2","article-title":"Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China","volume":"9","author":"Kruse","year":"2020","journal-title":"F1000Research"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"693","DOI":"10.4103\/ijo.IJO_639_20","article-title":"Therapeutic opportunities to manage COVID-19\/SARS-CoV-2 infection: Present and future","volume":"68","author":"Shetty","year":"2020","journal-title":"Indian J. Ophthalmol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.antiviral.2006.04.014","article-title":"Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction","volume":"74","author":"Ho","year":"2007","journal-title":"Antivir. Res."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Smith, M., and Smith, J.C. (2020). Repurposing therapeutics for COVID-19: Supercomputer-based docking to the SARS-CoV-2 viral spike protein and viral spike protein-human ACE2 interface. ChemRxiv, online ahead of print.","DOI":"10.26434\/chemrxiv.11871402"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1021\/acscentsci.0c00272","article-title":"Research and development on therapeutic agents and vaccines for COVID-19 and related human coronavirus diseases","volume":"6","author":"Liu","year":"2020","journal-title":"ACS Cent. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"7001","DOI":"10.1073\/pnas.2002589117","article-title":"Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells","volume":"117","author":"Matsuyama","year":"2020","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.bbrc.2004.04.083","article-title":"HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirus","volume":"318","author":"Yamamoto","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1248\/bpb.b12-00623","article-title":"Diarylheptanoids from Alnus japonica inhibit papain-like protease of severe acute respiratory syndrome coronavirus","volume":"35","author":"Park","year":"2012","journal-title":"Biol. Pharm. Bull."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.coviro.2016.01.001","article-title":"Type I interferons in viral control and immune regulation","volume":"16","author":"Teijaro","year":"2016","journal-title":"Curr. Opin. Virol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/nrd3974","article-title":"Challenges and approaches for the development of safer immunomodulatory biologics","volume":"12","author":"Sathish","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"113","DOI":"10.2174\/092986707779313444","article-title":"Structure and functions of influenza virus neuraminidase","volume":"14","author":"Gong","year":"2007","journal-title":"Curr. Med. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3389\/fmicb.2019.00039","article-title":"Influenza virus neuraminidase structure and functions","volume":"10","author":"McAuley","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s13337-015-0276-6","article-title":"Herbal plants and plant preparations as remedial approach for viral diseases","volume":"26","author":"Ganjhu","year":"2015","journal-title":"Virus Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3945\/an.114.007500","article-title":"Flavonoid-based therapies in the early management of neurodegenerative diseases","volume":"6","author":"Solanki","year":"2015","journal-title":"Adv. Nutr."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3177\/jnsv.63.51","article-title":"Association of dietary flavonoid intake with prevalence of type 2 diabetes mellitus and cardiovascular disease risk factors in Korean women aged\u2265 30 years","volume":"63","author":"Oh","year":"2017","journal-title":"J. Nutri. Sci. Vitaminol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e450","DOI":"10.1016\/S2542-5196(19)30212-8","article-title":"Associations between habitual flavonoid intake and hospital admissions for atherosclerotic cardiovascular disease: A prospective cohort study","volume":"3","author":"Dalgaard","year":"2019","journal-title":"Lancet Planet Health"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"454","DOI":"10.3945\/ajcn.111.016634","article-title":"Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults","volume":"95","author":"McCullough","year":"2012","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.clnesp.2017.03.004","article-title":"Flavonoid intake and mortality from cardiovascular disease and all causes: A meta-analysis of prospective cohort studies","volume":"20","author":"Kim","year":"2017","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"8919","DOI":"10.1039\/C9CC04084F","article-title":"Flavonoid\u2013alkylphospholipid conjugates elicit dual inhibition of cancer cell growth and lipid accumulation","volume":"55","author":"Zhou","year":"2019","journal-title":"Chem. Commun."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Loung, C.Y., Fernando, W., Rupasinghe, H.P., and Hoskin, D.W. (2019). Apple peel flavonoid fraction 4 suppresses breast cancer cell growth by cytostatic and cytotoxic mechanisms. Molecules, 24.","DOI":"10.3390\/molecules24183335"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1007\/s00394-019-01948-z","article-title":"A flavonoid-rich extract from bergamot juice prevents carcinogenesis in a genetic model of colorectal cancer, the Pirc rat (F344\/NTac-Apc am1137)","volume":"59","author":"Navarra","year":"2019","journal-title":"Eur. J. Nutr."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1021\/np030470h","article-title":"Antiviral Flavonoids from the Seeds of Aesculus chinensis","volume":"67","author":"Wei","year":"2004","journal-title":"J. Nat. Prod."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"T\u00e9llez, M.A., T\u00e9llez, A.N., V\u00e9lez, F., and Ulloa, J.C. (2015). In vitro antiviral activity against rotavirus and astrovirus infection exerted by substances obtained from Achyrocline bogotensis (Kunth) DC (Compositae). BMC Complement Altern. Med., 15.","DOI":"10.1186\/s12906-015-0949-0"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"197805","DOI":"10.1016\/j.virusres.2019.197805","article-title":"Quercetin pentaacetate inhibits in vitro human respiratory syncytial virus adhesion","volume":"276","author":"Lopes","year":"2020","journal-title":"Virus Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"111596","DOI":"10.1016\/j.biopha.2021.111596","article-title":"Antiviral activities of flavonoids","volume":"140","author":"Badshah","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"109211","DOI":"10.1016\/j.cbi.2020.109211","article-title":"Roles of flavonoids against coronavirus infection","volume":"328","author":"Russo","year":"2020","journal-title":"Chem. Biol. Interact."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jcv.2004.03.003","article-title":"In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds","volume":"31","author":"Chen","year":"2004","journal-title":"J. Clin. Virol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"11334","DOI":"10.1128\/JVI.78.20.11334-11339.2004","article-title":"Small molecules blocking the entry of severe acute respiratory syndrome coronavirus into host cells","volume":"78","author":"Yi","year":"2004","journal-title":"J. Virol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1080\/14756366.2016.1265519","article-title":"Evaluation of polyphenols from Broussonetiapapyrifera as coronavirus protease inhibitors","volume":"32","author":"Park","year":"2017","journal-title":"J. Enzy. Inhibit. Med. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1111\/cbdd.13604","article-title":"Characteristics of flavonoids as potent MERS-CoV 3C-like protease inhibitors","volume":"94","author":"Jo","year":"2019","journal-title":"Chem. Biol. Drug Design."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.2147\/IJN.S31379","article-title":"A facile inhibitor screening of SARS coronavirus N protein using nanoparticle-based RNA oligonucleotide","volume":"7","author":"Roh","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"6306","DOI":"10.1080\/07391102.2020.1796811","article-title":"Targeting SARS-CoV-2 spike protein of COVID-19 with naturally occurring phytochemicals: An in silico study for drug development","volume":"39","author":"Pandey","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Stoermer, M. (2020). Homology Models of Coronavirus 2019-nCoV 3CLpro Protease. Chemrxiv.","DOI":"10.26434\/chemrxiv.11637294"},{"key":"ref_101","unstructured":"WFMJ (2020, June 11). COVID-19 and Flavonoids: Study Examines How Infection Can Be Minimized. Available online: https:\/\/www.wfmj.com\/story\/42088783\/covid-19-and-flavonoids-study-examines-how-infection-can-be-minimized."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1007\/s10529-011-0845-8","article-title":"Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris","volume":"34","author":"Nguyen","year":"2012","journal-title":"Biotechnol. Lett."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1055\/s-0033-1360277","article-title":"Kaempferol derivatives as antiviral drugs against the 3A channel protein of coronavirus","volume":"80","author":"Schwarz","year":"2014","journal-title":"Planta Med."},{"key":"ref_104","first-page":"1","article-title":"Anti-inflammatory potential of Quercetin in COVID-19 treatment","volume":"18","author":"Boroujeni","year":"2021","journal-title":"J. Inflamm."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"586993","DOI":"10.3389\/fphar.2020.586993","article-title":"Potential natural products against respiratory viruses: A perspective to develop anti-COVID-19 medicines","volume":"11","author":"Omrani","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3277","DOI":"10.1021\/acs.jcim.0c00179","article-title":"Fast identification of possible drug treatment of coronavirus disease-19 (COVID-19) through computational drug repurposing study","volume":"73","author":"Wang","year":"2020","journal-title":"J. Chem. Inf. Model."},{"key":"ref_107","first-page":"11122","article-title":"An In Silico Screening on Piper nigrum, Syzygium aromaticum and Zingiber officinale roscoe derived compounds against SARS-CoV-2: A drug repurposing approach","volume":"11","author":"Pandey","year":"2021","journal-title":"Biointerface Res. Appl. Chem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1007\/s11030-020-10150-x","article-title":"Computational guided identification of a citrus flavonoid as potential inhibitor of SARS-CoV-2 main protease","volume":"25","author":"Gogoi","year":"2021","journal-title":"Mol. Divers."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3449","DOI":"10.1080\/07391102.2020.1766572","article-title":"Identification of bioactive molecules from tea plant as SARS-CoV-2 main protease inhibitors","volume":"39","author":"Bhardwaj","year":"2021","journal-title":"J. Biomol. Struc. Dyn."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.3389\/fimmu.2020.01451","article-title":"Quercetin and vitamin C: An experimental, synergistic therapy for the prevention and treatment of SARS-CoV-2 related disease (COVID-19)","volume":"11","author":"ColungaBiancatelli","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"6463","DOI":"10.1080\/07391102.2021.1885495","article-title":"Anti-HIV-drug and phyto-flavonoid combination against SARS-CoV-2: A molecular docking-simulation base assessment","volume":"40","author":"Swain","year":"2021","journal-title":"J. Biomol. Struc. Dyn."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"6839","DOI":"10.1038\/s41598-020-63913-9","article-title":"Computer-aided synthesis of dapsone-phytochemical conjugates against dapsone-resistant Mycobacterium leprae","volume":"10","author":"Swain","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"173448","DOI":"10.1016\/j.ejphar.2020.173448","article-title":"In silico pharmacokinetic and molecular docking studies of natural flavonoids and synthetic indole chalcones against essential proteins of SARS-CoV-2","volume":"886","author":"Vijayakumar","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Ngwa, W., Kumar, R., Thompson, D., Lyerly, W., Moore, R., Reid, T.E., Lowe, H., and Toyang, N. (2020). potential of flavonoid-inspired phytomedicines against COVID-19. Molecules, 25.","DOI":"10.3390\/molecules25112707"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"19570","DOI":"10.1039\/D0RA03582C","article-title":"Molecular docking reveals the potential of Salvadorapersica flavonoids to inhibit COVID-19 virus main protease","volume":"10","author":"Owis","year":"2020","journal-title":"RSC Adv."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"106012","DOI":"10.1016\/j.ijantimicag.2020.106012","article-title":"Computational screening of antagonist against the SARS-CoV-2 (COVID-19) coronavirus by molecular docking","volume":"56","author":"Yu","year":"2020","journal-title":"Int. J. Antimicrob. Agents."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1002\/jmv.25761","article-title":"The potential chemical structure of anti-SARS-CoV-2 RNA-dependent RNA polymerase","volume":"92","author":"Lung","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Mishra, R.C., Kumari, R., Yadav, S., and Yadav, J.P. (2020). Antiviral potential of phytoligands against chymotrypsin-like protease of COVID-19 virus using molecular docking studies: An optimistic approach. Preprints, online ahead of print.","DOI":"10.21203\/rs.3.rs-23956\/v1"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Tallei, T.E., Tumilaar, S.G., Niode, N.J., Fatimawali, F., Kepel, B.J., Idroes, R., and Effendi, Y. (2020). Potential of plant bioactive compounds as SARS-CoV-2 main protease (Mpro) and spike (S) glycoprotein inhibitors: A molecular docking study. Preprints, 2020040102.","DOI":"10.20944\/preprints202004.0102.v1"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Utomo, R.Y., and Meiyanto, E. (2020). Revealing the potency of citrus and galangal constituents to halt SARS-CoV-2 infection. Preprints, 2020030214.","DOI":"10.20944\/preprints202003.0214.v1"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Basu, A., Sarkar, A., and Maulik, U. (2020). Computational approach for the design of potential spike protein binding natural compounds in SARS-CoV2. Res. Sq.","DOI":"10.21203\/rs.3.rs-33181\/v1"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Chauhan, A., and Kalra, S. (2020). Identification of potent COVID-19 main protease (Mpro) inhibitors from flavonoids. Res. Sq.","DOI":"10.21203\/rs.3.rs-34497\/v1"},{"key":"ref_123","unstructured":"Srivastava, A.K., Kumar, A., and Misra, N. (2020). On the inhibition of COVID-19 protease by Indian herbal plants: An in silico investigation. arXiv."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/19\/6374\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:40:18Z","timestamp":1760143218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/19\/6374"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,27]]},"references-count":123,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["molecules27196374"],"URL":"https:\/\/doi.org\/10.3390\/molecules27196374","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,27]]}}}