{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T02:25:43Z","timestamp":1770085543768,"version":"3.49.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-25217-8","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T12:47:23Z","timestamp":1770036443000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioactive galloylquinic acids from Copaifera lucens as dual inhibitors of SARS-CoV-2 Spike and RdRp proteins"],"prefix":"10.1038","volume":"16","author":[{"given":"Rasha M.","family":"El-Morsi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lamiaa A.","family":"Al-Madboly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jairo K.","family":"Bastos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaimaa M.","family":"Aboukhatwa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samah A.","family":"Nasr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doaa A.","family":"Ghareeb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heba A.","family":"Ramadan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Kushkevych","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed A.","family":"Abd El-Salam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"issue":"7","key":"25217_CR1","doi-asserted-by":"publisher","first-page":"e453","DOI":"10.1016\/S1473-3099(23)00815-0","volume":"24","author":"HM Machkovech","year":"2024","unstructured":"Machkovech, H. M. et al. Persistent SARS-CoV-2 infection: significance and implications. Lancet Infect. Dis. 24(7), e453\u2013e462 (2024).","journal-title":"Lancet Infect. Dis."},{"key":"25217_CR2","doi-asserted-by":"crossref","unstructured":"Boyd, H. A. et al. SARS-CoV-2 infection and long-term risk of cardiovascular and renal morbidity. medRxiv. 2025.01.14.25320050 (2025).","DOI":"10.1101\/2025.01.14.25320050"},{"key":"25217_CR3","doi-asserted-by":"publisher","first-page":"1339660","DOI":"10.3389\/fimmu.2024.1339660","volume":"15","author":"L Chen","year":"2024","unstructured":"Chen, L. et al. Potential immune evasion of the severe acute respiratory syndrome coronavirus 2 Omicron variants. Front. Immunol. 15, 1339660 (2024).","journal-title":"Front. Immunol."},{"issue":"8","key":"25217_CR4","doi-asserted-by":"publisher","first-page":"3013","DOI":"10.1002\/ptr.7463","volume":"36","author":"K Leka","year":"2022","unstructured":"Leka, K. et al. In vitro antiviral activity against SARS-CoV-2 of common herbal medicinal extracts and their bioactive compounds. Phytother Res. 36(8), 3013\u20133015 (2022).","journal-title":"Phytother Res."},{"issue":"3","key":"25217_CR5","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/s41422-020-0282-0","volume":"30","author":"M Wang","year":"2020","unstructured":"Wang, M. et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell. Res. 30(3), 269\u2013271 (2020).","journal-title":"Cell. Res."},{"issue":"1","key":"25217_CR6","doi-asserted-by":"publisher","first-page":"10896","DOI":"10.1038\/s41598-022-14558-3","volume":"12","author":"A Boadu","year":"2022","unstructured":"Boadu, A. et al. Repurposing antiviral phytochemicals from the leaf extracts of Spondias mombin (Linn) towards the identification of potential SARSCOV-2 inhibitors. Sci. Rep. 12(1), 10896 (2022).","journal-title":"Sci. Rep."},{"key":"25217_CR7","doi-asserted-by":"publisher","first-page":"120497","DOI":"10.1016\/j.lfs.2022.120497","volume":"299","author":"MA Abd El-Salam","year":"2022","unstructured":"Abd El-Salam, M. A. et al. Novel antitumor activity of the combined treatment of galloylquinic acid compounds with doxorubicin in solid Ehrlich carcinoma model via the Notch signaling pathway modulation. Life Sci. 299, 120497 (2022).","journal-title":"Life Sci."},{"issue":"5","key":"25217_CR8","doi-asserted-by":"publisher","first-page":"e02724","DOI":"10.1128\/spectrum.02724-21","volume":"10","author":"LA Al-Madboly","year":"2022","unstructured":"Al-Madboly, L. A. et al. Novel preclinical study of galloylquinic acid compounds from Copaifera lucens with potent antifungal activity against vaginal candidiasis induced in a murine model via multitarget modes of action. Microbiol. Spectr. 10(5), e02724\u2013e02721 (2022).","journal-title":"Microbiol. Spectr."},{"issue":"5","key":"25217_CR9","doi-asserted-by":"publisher","first-page":"724","DOI":"10.2174\/092986713804999349","volume":"20","author":"CO Junior","year":"2013","unstructured":"Junior, C. O. et al. Synthesis and HIV-1 inhibitory activities of dicaffeoyl and digalloyl esters of quinic acid derivatives. Curr. Med. Chem. 20(5), 724\u2013733 (2013).","journal-title":"Curr. Med. Chem."},{"issue":"4","key":"25217_CR10","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1021\/np50064a016","volume":"52","author":"M Nishizawa","year":"1989","unstructured":"Nishizawa, M. et al. Anti-AIDS agents, 1. Isolation and characterization of four new tetragalloylquinic acids as a new class of HIV reverse transcriptase inhibitors from tannic acid. J. Nat. Prod. 52(4), 762\u2013768 (1989).","journal-title":"J. Nat. Prod."},{"issue":"2","key":"25217_CR11","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1080\/10575639608043252","volume":"8","author":"HR Bokesch","year":"1996","unstructured":"Bokesch, H. R. et al. HIV-Inhibitory gallotannins from Lepidobotrys staudtii. Nat. Prod. Lett. 8(2), 133\u2013136 (1996).","journal-title":"Nat. Prod. Lett."},{"key":"25217_CR12","doi-asserted-by":"publisher","first-page":"105820","DOI":"10.1016\/j.fitote.2024.105820","volume":"173","author":"CM Rodrigues","year":"2024","unstructured":"Rodrigues, C. M. et al. A potential antiviral against COVID-19 obtained from Byrsonima coccolobifolia leaves extract. Fitoterapia 173, 105820 (2024).","journal-title":"Fitoterapia"},{"key":"25217_CR13","doi-asserted-by":"crossref","unstructured":"Abd El-Salam, M. A. et al. Antiurolithic activity and biotransformation of galloylquinic acids by Aspergillus alliaceus ATCC10060, Aspergillus brasiliensis ATCC 16404, and Cunninghamella elegans ATCC 10028b. Biocatal. Agric. Biotechnol. 18\u00a0(2019).","DOI":"10.1016\/j.bcab.2019.01.050"},{"issue":"4","key":"25217_CR14","doi-asserted-by":"publisher","first-page":"p1609","DOI":"10.1021\/acs.jmedchem.7b01566","volume":"61","author":"M Abd El-Salam","year":"2018","unstructured":"Abd El-Salam, M. et al. The synthesized plant metabolite 3,4,5-tri-O-galloylquinic acid methyl ester inhibits calcium oxalate crystal growth in a drosophila model, downregulates renal cell surface annexin A1 expression, and decreases crystal adhesion to cells. J. Med. Chem. 61(4), p1609\u20131621 (2018).","journal-title":"J. Med. Chem."},{"issue":"1\u20132","key":"25217_CR15","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","volume":"65","author":"T Mosmann","year":"1983","unstructured":"Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods. 65(1\u20132), 55\u201363 (1983).","journal-title":"J. Immunol. Methods"},{"key":"25217_CR16","doi-asserted-by":"crossref","unstructured":"Mostafa, A. et al. FDA-approved drugs with potent in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2. Pharmaceuticals. 13(12) (2020).","DOI":"10.3390\/ph13120443"},{"issue":"5","key":"25217_CR17","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1128\/AAC.17.5.865","volume":"17","author":"FG Hayden","year":"1980","unstructured":"Hayden, F. G., Cote, K. M. & Douglas, R. G. Jr. Plaque inhibition assay for drug susceptibility testing of influenza viruses. Antimicrob. Agents Chemother. 17(5), 865\u2013870 (1980).","journal-title":"Antimicrob. Agents Chemother."},{"issue":"47","key":"25217_CR18","doi-asserted-by":"publisher","first-page":"29267","DOI":"10.1039\/D1RA05268C","volume":"11","author":"D Elebeedy","year":"2021","unstructured":"Elebeedy, D. et al. Anti-SARS-CoV-2 activities of tanshinone IIA, carnosic acid, rosmarinic acid, salvianolic acid, baicalein, and glycyrrhetinic acid between computational and in vitro insights. RSC Adv. 11(47), 29267\u201329286 (2021).","journal-title":"RSC Adv."},{"issue":"9","key":"25217_CR19","first-page":"556","volume":"20","author":"J Zhang","year":"1995","unstructured":"Zhang, J. et al. Antiviral activity of tannin from the pericarp of Punica granatum L. against genital herpes virus in vitro. Zhongguo Zhong Yao Za Zhi. 20(9), 556\u2013558, 576, inside backcover (1995).","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"issue":"9","key":"25217_CR20","doi-asserted-by":"publisher","first-page":"2854","DOI":"10.1128\/AAC.46.9.2854-2864.2002","volume":"46","author":"YC Kuo","year":"2002","unstructured":"Kuo, Y. C. et al. Samarangenin B from Limonium sinense suppresses herpes simplex virus type 1 replication in vero cells by regulation of viral macromolecular synthesis. Antimicrob. Agents Chemother. 46(9), 2854\u20132864 (2002).","journal-title":"Antimicrob. Agents Chemother."},{"issue":"6","key":"25217_CR21","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1078\/094471103322331467","volume":"10","author":"A Schuhmacher","year":"2003","unstructured":"Schuhmacher, A., Reichling, J. & Schnitzler, P. Virucidal effect of peppermint oil on the enveloped viruses herpes simplex virus type 1 and type 2 in vitro. Phytomedicine 10(6), 504\u2013510 (2003).","journal-title":"Phytomedicine"},{"key":"25217_CR22","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/s41048-015-0006-z","volume":"1","author":"L Cao","year":"2015","unstructured":"Cao, L. et al. A comprehensive procedure for antiviral inhibitor discovery using EV71 as an example. Biophys. Rep. 1, 81\u201389 (2015).","journal-title":"Biophys. Rep."},{"issue":"6\u20137","key":"25217_CR23","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1078\/094471103322331467","volume":"10","author":"A Schuhmacher","year":"2003","unstructured":"Schuhmacher, A., Reichling, J. & Schnitzler, P. Virucidal effect of peppermint oil on the enveloped viruses herpes simplex virus type 1 and type 2 in vitro. Phytomedicine 10(6\u20137), 504\u2013510 (2003).","journal-title":"Phytomedicine"},{"key":"25217_CR24","unstructured":"ULC, C. C. G. Molecular Operating Environment (MOE), 2020.09, 1010 Sherbooke St. West, Suite #910, Montreal, QC, Canada, H3A 2R7. (2022)."},{"issue":"6496","key":"25217_CR25","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1126\/science.abc2241","volume":"368","author":"Y Wu","year":"2020","unstructured":"Wu, Y. et al. A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2. Science 368(6496), 1274\u20131278 (2020).","journal-title":"Science"},{"issue":"5\u20136","key":"25217_CR26","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1002\/(SICI)1096-987X(199604)17:5\/6<490::AID-JCC1>3.0.CO;2-P","volume":"17","author":"TA Halgren","year":"1996","unstructured":"Halgren, T. A. Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94. J. Comput. Chem. 17(5\u20136), 490\u2013519 (1996).","journal-title":"J. Comput. Chem."},{"issue":"6","key":"25217_CR27","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1007\/s10822-012-9570-1","volume":"26","author":"CR Corbeil","year":"2012","unstructured":"Corbeil, C. R., Williams, C. I. & Labute, P. Variability in docking success rates due to dataset preparation. J. Comput. Aided Mol. Des. 26(6), 775\u2013786 (2012).","journal-title":"J. Comput. Aided Mol. Des."},{"key":"25217_CR28","unstructured":"Biovia, D. S. Discovery Studio Visualizer, Release 2021, San Diego: Dassault Syst\u00e8mes.(2021)."},{"issue":"6498","key":"25217_CR29","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1126\/science.abc1560","volume":"368","author":"W Yin","year":"2020","unstructured":"Yin, W. et al. Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science 368(6498), 1499\u20131504 (2020).","journal-title":"Science"},{"key":"25217_CR30","doi-asserted-by":"publisher","first-page":"114367","DOI":"10.1016\/j.biopha.2023.114367","volume":"162","author":"SMR Hashemian","year":"2023","unstructured":"Hashemian, S. M. R. et al. Paxlovid (nirmatrelvir\/ritonavir): A new approach to covid-19 therapy? Biomed. Pharmacother. 162, 114367 (2023).","journal-title":"Biomed. Pharmacother"},{"key":"25217_CR31","doi-asserted-by":"crossref","unstructured":"Carlin, A. F. et al. Virologic and immunologic characterization of COVID-19 recrudescence after nirmatrelvir\/ritonavir treatment. Res. Sq. (2022).","DOI":"10.21203\/rs.3.rs-1662783\/v1"},{"issue":"1","key":"25217_CR32","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1186\/s12906-017-1962-2","volume":"17","author":"M Di Nunzio","year":"2017","unstructured":"Di Nunzio, M. et al. Is cytotoxicity a determinant of the different in vitro and in vivo effects of bioactives? BMC Complement. Altern. Med. 17(1), 453 (2017).","journal-title":"BMC Complement. Altern. Med."},{"key":"25217_CR33","doi-asserted-by":"crossref","unstructured":"Baeshen, M. N. et al. Assaying for antiviral activity of the folkloric medicinal desert plant Rhazya stricta on coronavirus SARS-CoV-2. Biotechnol. Biotechnol. Equip. 36(1), 68\u201374 (2022).","DOI":"10.1080\/13102818.2022.2047107"},{"key":"25217_CR34","doi-asserted-by":"crossref","unstructured":"Pizzorno, A. et al. In vitro evaluation of antiviral activity of single and combined repurposable drugs against SARS-CoV-2. Antivir. Res. 181, 104878 (2020).","DOI":"10.1016\/j.antiviral.2020.104878"},{"key":"25217_CR35","doi-asserted-by":"crossref","unstructured":"Attallah, N. G. M. et al. Promising antiviral activity of Agrimonia pilosa phytochemicals against severe acute respiratory syndrome coronavirus 2 supported with in vivo mice study. Pharmaceuticals (Basel) 14(12), 1313 (2021).","DOI":"10.3390\/ph14121313"},{"key":"25217_CR36","doi-asserted-by":"crossref","unstructured":"Marahatha, R. et al. In silico study of alkaloids neferine and berbamine potentially inhibiting the SARS-CoV-2 RNA-dependent RNA polymerase. J. Chem. 2022(1), 7548802 (2022).","DOI":"10.1155\/2022\/7548802"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-25217-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-25217-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-25217-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T12:47:25Z","timestamp":1770036445000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-25217-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,2]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["25217"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-25217-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,2]]},"assertion":[{"value":"16 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 February 2026","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":"4521"}}