{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T02:33:06Z","timestamp":1793241186137,"version":"4.5.0"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Start-Up Funds","award":["172803"],"award-info":[{"award-number":["172803"]}]},{"name":"National Science Foundation","award":["REU 2150363"],"award-info":[{"award-number":["REU 2150363"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-27374-2","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T13:06:33Z","timestamp":1764248793000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Improving quercetin solubility via structural modification enhances dual-target coronavirus entry: an integrated in-vitro and in-silico study"],"prefix":"10.1038","volume":"15","author":[{"given":"Milad","family":"Torabfam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gizem","family":"Celebi Torabfam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Osonga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiano","family":"Dias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omowunmi","family":"Sadik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"27374_CR1","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1001\/jamacardio.2020.1282","volume":"5","author":"C Bavishi","year":"2020","unstructured":"Bavishi, C., Maddox, T. M. & Messerli, F. H. Coronavirus disease 2019 (COVID-19) infection and Renin Angiotensin system blockers. JAMA Cardiol 5, 745 (2020).","journal-title":"JAMA Cardiol"},{"key":"27374_CR2","doi-asserted-by":"publisher","first-page":"244","DOI":"10.3390\/v12020244","volume":"12","author":"J Xu","year":"2020","unstructured":"Xu, J. et al. Systematic comparison of two Animal-to-human transmitted human coronaviruses: SARS-CoV-2 and SARS-CoV. Viruses 12, 244 (2020).","journal-title":"Viruses"},{"key":"27374_CR3","doi-asserted-by":"publisher","first-page":"27935","DOI":"10.1039\/D4RA04728A","volume":"14","author":"ARI Morsy","year":"2024","unstructured":"Morsy, A. R. I. et al. Antiviral activity of pyrazole derivatives bearing a hydroxyquinoline scaffold against SARS-CoV-2, HCoV-229E, MERS-CoV, and IBV propagation. RSC Adv 14, 27935\u201327947 (2024).","journal-title":"RSC Adv"},{"key":"27374_CR4","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1080\/17576180.2024.2411920","volume":"16","author":"AN Cimen","year":"2024","unstructured":"Cimen, A. N. et al. Development of Pseudotyped VSV-SARS-CoV-2 spike variants for the assessment of neutralizing antibodies. Bioanalysis 16, 1167\u20131177 (2024).","journal-title":"Bioanalysis"},{"key":"27374_CR5","doi-asserted-by":"publisher","first-page":"2289007","DOI":"10.1080\/14756366.2023.2289007","volume":"39","author":"Z Ferjancic","year":"2024","unstructured":"Ferjancic, Z. et al. Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies. J. Enzyme Inhib. Med. Chem. 39, 2289007 (2024).","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"27374_CR6","doi-asserted-by":"publisher","first-page":"e01008","DOI":"10.1002\/slct.202501008","volume":"10","author":"C Peron","year":"2025","unstructured":"Peron, C. et al. Synthesis and chemical characterization of chloroquine, hydroxychloroquine, zinc, and cinnamic acid organocomplexes: Potential drug candidates for SARS-CoV-2 treatment and microbial control. ChemistrySelect 10, e01008 (2025).","journal-title":"ChemistrySelect"},{"key":"27374_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.algal.2024.103468","volume":"79","author":"HSH Munawaroh","year":"2024","unstructured":"Munawaroh, H. S. H. et al. In silico antiviral properties of Spirulina platensis phycobiliprotein and phycobilin as natural inhibitor for SARS-CoV-2. Algal Res 79, 103468 (2024).","journal-title":"Algal Res"},{"key":"27374_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.tmaid.2020.101646","volume":"35","author":"DC Hall","year":"2020","unstructured":"Hall, D. C. & Ji, H.-F. A search for medications to treat COVID-19 via in silico molecular docking models of the SARS-CoV-2 spike glycoprotein and 3CL protease. Travel. Med. Infect. Dis. 35, 101646 (2020).","journal-title":"Travel. Med. Infect. Dis."},{"key":"27374_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.hermed.2025.101057","volume":"54","author":"BR Kumar","year":"2025","unstructured":"Kumar, B. R., Kumar, K. M., Sen, S. & Oruganti, S. Cocrystal of flavonoids as potential phyto-therapeutic agents against SARS-CoV-2: A scoping review. J. Herb. Med. 54, 101057 (2025).","journal-title":"J. Herb. Med."},{"key":"27374_CR10","doi-asserted-by":"publisher","first-page":"3980","DOI":"10.3390\/molecules25173980","volume":"25","author":"M Muchtaridi","year":"2020","unstructured":"Muchtaridi, M., Fauzi, M., Khairul Ikram, N. K., Mohd Gazzali, A. & Wahab, H. A. Natural flavonoids as potential angiotensin-converting enzyme 2 inhibitors for anti-SARS-CoV-2. Molecules 25, 3980 (2020).","journal-title":"Molecules"},{"key":"27374_CR11","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1080\/17460441.2023.2241366","volume":"18","author":"SR Alizadeh","year":"2023","unstructured":"Alizadeh, S. R., Savadkouhi, N. & Ebrahimzadeh, M. A. Drug design strategies that aim to improve the low solubility and poor bioavailability conundrum in quercetin derivatives. Expert. Opin. Drug. Discov. 18, 1117\u20131132 (2023).","journal-title":"Expert. Opin. Drug. Discov."},{"key":"27374_CR12","doi-asserted-by":"publisher","first-page":"2300898","DOI":"10.1002\/mnfr.202300898","volume":"68","author":"T Li","year":"2024","unstructured":"Li, T. et al. Dietary flavonoid quercetin supplement promotes antiviral innate responses against vesicular stomatitis virus infection by Reshaping the Bacteriome and host metabolome in mice. Mol. Nutr. Food Res. 68, 2300898 (2024).","journal-title":"Mol. Nutr. Food Res."},{"key":"27374_CR13","doi-asserted-by":"publisher","first-page":"31855","DOI":"10.1039\/D2RA05478G","volume":"12","author":"FJ Osonga","year":"2022","unstructured":"Osonga, F. J., Eshun, G. B. & Sadik, O. A. Ligand effect on controlling the synthesis of branched gold nanomaterials against fusarium wilt diseases. RSC Adv. 12, 31855\u201331868 (2022).","journal-title":"RSC Adv."},{"key":"27374_CR14","doi-asserted-by":"publisher","first-page":"8133","DOI":"10.3390\/molecules27238133","volume":"27","author":"DK Isika","year":"2022","unstructured":"Isika, D. K. & Sadik, O. A. Selective structural derivatization of Flavonoid acetamides significantly impacts their bioavailability and antioxidant properties. Molecules 27, 8133 (2022).","journal-title":"Molecules"},{"key":"27374_CR15","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.1016\/j.tetlet.2017.02.085","volume":"58","author":"FJ Osonga","year":"2017","unstructured":"Osonga, F. J. et al. Synthesis and characterization of novel flavonoid derivatives via sequential phosphorylation of quercetin. Tetrahedron. Lett. 58, 1474\u20131479 (2017).","journal-title":"Tetrahedron. Lett."},{"key":"27374_CR16","doi-asserted-by":"publisher","first-page":"4649","DOI":"10.1039\/C7RA13480K","volume":"8","author":"FJ Osonga","year":"2018","unstructured":"Osonga, F. J. et al. Flavonoid-derived anisotropic silver nanoparticles inhibit growth and change the expression of virulence genes in Escherichia coli SM10. RSC Adv. 8, 4649\u20134661 (2018).","journal-title":"RSC Adv."},{"key":"27374_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.elecom.2025.107950","volume":"175","author":"M Torabfam","year":"2025","unstructured":"Torabfam, M., Xue, H., Osonga, F. & Sadik, O. Elucidating the electrochemical behavior and reaction pathway of 1,4-Dioxane: An integrated experimental and simulation approach. Electrochem. Commun. 175, 107950 (2025).","journal-title":"Electrochem. Commun."},{"issue":"3","key":"27374_CR18","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1021\/acsestwater.4c00912","volume":"5","author":"M Torabfam","year":"2025","unstructured":"Torabfam, M., Osonga, F., Young, Q. & Sadik, O. Scalable electrochemical detection and degradation of 1,4-dioxane in water and wastewater: A Core-shell bimetallic nanocatalyst and simulation study. ACS ES&T Water. 5(3), 1158\u20131172. https:\/\/doi.org\/10.1021\/acsestwater.4c00912 (2025).","journal-title":"ACS ES&T Water."},{"key":"27374_CR19","doi-asserted-by":"publisher","first-page":"5472","DOI":"10.1039\/C4AN00931B","volume":"139","author":"SK Mwilu","year":"2014","unstructured":"Mwilu, S. K., Okello, V. A., Osonga, F. J., Miller, S. & Sadik, O. A. A new substrate for alkaline phosphatase based on quercetin pentaphosphate. Analyst 139, 5472\u20135481 (2014).","journal-title":"Analyst"},{"key":"27374_CR20","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1039\/C5EM00580A","volume":"18","author":"VA Okello","year":"2016","unstructured":"Okello, V. A., Osonga, F. J., Knipfing, M. T., Bushlyar, V. & Sadik, O. A. Reactivity, characterization of reaction products and immobilization of lead in water and sediments using quercetin pentaphosphate. Environ. Sci. Process Impacts 18, 306\u2013313 (2016).","journal-title":"Environ. Sci. Process Impacts"},{"key":"27374_CR21","doi-asserted-by":"publisher","first-page":"2390","DOI":"10.3390\/molecules30112390","volume":"30","author":"Y Liu","year":"2025","unstructured":"Liu, Y., Yan, Q. & Hu, C. Enhancing oral absorption of quercetin through multifactorial synergies in crystal dispersion systems. Molecules 30, 2390 (2025).","journal-title":"Molecules"},{"key":"27374_CR22","volume-title":"Design and synthesis of a novel class of flavonoid derivatives via sequential phosphorylation and its application for greener nanoparticle synthesis","author":"FJ Osonga","year":"2017","unstructured":"Osonga, F. J. Design and synthesis of a novel class of flavonoid derivatives via sequential phosphorylation and its application for greener nanoparticle synthesis (Binghamton University, New York, 2017)."},{"key":"27374_CR23","doi-asserted-by":"publisher","first-page":"125698","DOI":"10.1016\/j.jssc.2025.125698","volume":"353","author":"GP de Costa","year":"2026","unstructured":"de Costa, G. P. et al. Enhancing Norfloxacin\u2019s solubility: Development and characterization of new solid-state forms with p-aminobenzoic acid. J. Solid State Chem. 353, 125698 (2026).","journal-title":"J. Solid State Chem."},{"key":"27374_CR24","doi-asserted-by":"publisher","first-page":"2349","DOI":"10.1111\/ijfs.16963","volume":"59","author":"L Pei","year":"2024","unstructured":"Pei, L. et al. Effect of phosphorylation of long-chain inulin on the rheological properties of wheat flour doughs with different gluten. Int. J. Food Sci. Technol. 59, 2349\u20132360 (2024).","journal-title":"Int. J. Food Sci. Technol."},{"key":"27374_CR25","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1007\/s11418-022-01660-z","volume":"77","author":"R Morimoto","year":"2023","unstructured":"Morimoto, R. et al. Anti-influenza A virus activity of flavonoids in vitro: a structure\u2013activity relationship. J. Nat. Med. 77, 219\u2013227 (2023).","journal-title":"J. Nat. Med."},{"key":"27374_CR26","doi-asserted-by":"publisher","first-page":"788","DOI":"10.4236\/jbise.2013.68096","volume":"06","author":"S-F Chen","year":"2013","unstructured":"Chen, S.-F. & Danao, M.-G.C. Predictive models of ethanol concentrations in simulated exhaled breath and exhaled breath condensate under varied sampling conditions. J. Biomed. Sci. Eng. 06, 788\u2013795 (2013).","journal-title":"J. Biomed. Sci. Eng."},{"key":"27374_CR27","doi-asserted-by":"publisher","first-page":"3212","DOI":"10.1039\/D4MD00286E","volume":"15","author":"RJZ Rosal","year":"2024","unstructured":"Rosal, R. J. Z. & Paderes, M. C. Inhibiting SARS-CoV-2 viral entry by targeting spike:ACE2 interaction with O -modified quercetin derivatives. RSC Med. Chem. 15, 3212\u20133222 (2024).","journal-title":"RSC Med. Chem."},{"key":"27374_CR28","doi-asserted-by":"publisher","first-page":"13398","DOI":"10.1038\/s41598-023-40160-2","volume":"13","author":"PC Agu","year":"2023","unstructured":"Agu, P. C. et al. Molecular docking as a tool for the discovery of molecular targets of nutraceuticals in diseases management. Sci. Rep. 13, 13398 (2023).","journal-title":"Sci. Rep."},{"key":"27374_CR29","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1038\/cr.2013.92","volume":"23","author":"N Wang","year":"2013","unstructured":"Wang, N. et al. Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4. Cell Res. 23, 986\u2013993 (2013).","journal-title":"Cell Res."},{"key":"27374_CR30","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1016\/j.str.2024.08.005","volume":"32","author":"W Cui","year":"2024","unstructured":"Cui, W., Duan, Y., Gao, Y., Wang, W. & Yang, H. Structural review of SARS-CoV-2 antiviral targets. Structure 32, 1301\u20131321 (2024).","journal-title":"Structure"},{"key":"27374_CR31","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1021\/acs.cgd.8b01630","volume":"19","author":"R Thakuria","year":"2019","unstructured":"Thakuria, R., Nath, N. K. & Saha, B. K. The nature and applications of \u03c0\u2013\u03c0 Interactions: A perspective. Cryst. Growth. Des. 19, 523\u2013528 (2019).","journal-title":"Cryst. Growth. Des."},{"key":"27374_CR32","doi-asserted-by":"publisher","first-page":"25046","DOI":"10.1039\/D0RA04559D","volume":"10","author":"D Isika","year":"2020","unstructured":"Isika, D., \u00c7e\u015fme, M., Osonga, F. J. & Sadik, O. A. Novel quercetin and apigenin-acetamide derivatives: design, synthesis, characterization, biological evaluation and molecular docking studies. RSC Adv 10, 25046\u201325058 (2020).","journal-title":"RSC Adv"},{"key":"27374_CR33","doi-asserted-by":"publisher","first-page":"5061","DOI":"10.1021\/jm100112j","volume":"53","author":"C Bissantz","year":"2010","unstructured":"Bissantz, C., Kuhn, B. & Stahl, M. A Medicinal Chemist\u2019s Guide to Molecular Interactions. J Med Chem 53, 5061\u20135084 (2010).","journal-title":"J Med Chem"},{"key":"27374_CR34","unstructured":"Key Concepts, P. S. Organic Chemistry Study Guide. (ScienceDirect, 2015)."},{"key":"27374_CR35","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/0001-8686(95)00287-1","volume":"64","author":"K Shinoda","year":"1996","unstructured":"Shinoda, K., Carlsson, A. & Lindman, B. On the importance of hydroxyl groups in the polar head-group of nonionic surfactants and membrane lipids. Adv. Colloid. Interface Sci. 64, 253\u2013271 (1996).","journal-title":"Adv. Colloid. Interface Sci."},{"key":"27374_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113622","volume":"223","author":"G-N Zhang","year":"2021","unstructured":"Zhang, G.-N. et al. Discovery and optimization of 2-((1H-indol-3-yl)thio)-N-benzyl-acetamides as novel SARS-CoV-2 RdRp inhibitors. Eur. J. Med. Chem. 223, 113622 (2021).","journal-title":"Eur. J. Med. Chem."},{"key":"27374_CR37","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.3390\/v15051145","volume":"15","author":"E De Clercq","year":"2023","unstructured":"De Clercq, E. Hydrogen bonding (base pairing) in antiviral activity. Viruses 15, 1145 (2023).","journal-title":"Viruses"},{"key":"27374_CR38","doi-asserted-by":"crossref","unstructured":"Lipinski, C. A., Lombardo, F., Dominy, B. W. & Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings 1PII of original article: S0169\u2013409X(96)00423\u20131. The article was originally published in Advanced Drug Delivery Reviews 23 (1997) 3\u201325. 1. Adv Drug Deliv Rev 46, 3\u201326 (2001).","DOI":"10.1016\/S0169-409X(00)00129-0"},{"key":"27374_CR39","doi-asserted-by":"publisher","first-page":"717","DOI":"10.3390\/ph16050717","volume":"16","author":"T Maliar","year":"2023","unstructured":"Maliar, T. et al. The adapted POM analysis of Avenanthramides in silico. Pharmaceuticals 16, 717 (2023).","journal-title":"Pharmaceuticals"},{"key":"27374_CR40","doi-asserted-by":"publisher","DOI":"10.1016\/j.molliq.2021.117761","volume":"344","author":"AN Khalilov","year":"2021","unstructured":"Khalilov, A. N. et al. Cytotoxic effect, spectroscopy, DFT, enzyme inhibition, and moleculer docking studies of some novel mesitylaminopropanols: Antidiabetic and anticholinergics and anticancer potentials. J Mol Liq 344, 117761 (2021).","journal-title":"J Mol Liq"},{"key":"27374_CR41","doi-asserted-by":"publisher","first-page":"3900","DOI":"10.3390\/molecules26133900","volume":"26","author":"MA Khazeei Tabari","year":"2021","unstructured":"Khazeei Tabari, M. A., Iranpanah, A., Bahramsoltani, R. & Rahimi, R. Flavonoids as promising antiviral agents against SARS-CoV-2 infection: A mechanistic review. Molecules 26, 3900 (2021).","journal-title":"Molecules"},{"key":"27374_CR42","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1007\/s10822-012-9557-y","volume":"26","author":"G Schaftenaar","year":"2012","unstructured":"Schaftenaar, G. & de Vlieg, J. Quantum mechanical polar surface area. J. Comput. Aided. Mol. Des. 26, 311\u2013318 (2012).","journal-title":"J. Comput. Aided. Mol. Des."},{"key":"27374_CR43","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.3390\/ijms20061402","volume":"20","author":"A Di Pizio","year":"2019","unstructured":"Di Pizio, A., Behrens, M. & Krautwurst, D. Beyond the flavour: the potential druggability of chemosensory G protein-coupled receptors. Int J Mol Sci 20, 1402 (2019).","journal-title":"Int J Mol Sci"},{"key":"27374_CR44","unstructured":"https:\/\/www.molinspiration.com\/."},{"key":"27374_CR45","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2022.132688","volume":"1258","author":"M Rbaa","year":"2022","unstructured":"Rbaa, M. et al. Synthesis, characterization and bioactivity of novel 8-hydroxyquinoline derivatives: Experimental, molecular docking, DFT and POM analyses. J Mol Struct 1258, 132688 (2022).","journal-title":"J Mol Struct"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-27374-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-27374-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-27374-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T16:03:02Z","timestamp":1764864182000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-27374-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,27]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["27374"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-27374-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,27]]},"assertion":[{"value":"19 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"43140"}}