{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T20:42:29Z","timestamp":1793133749400,"version":"4.5.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32202801"],"award-info":[{"award-number":["32202801"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016073","name":"Key Technologies Research and Development Program of Anhui Province","doi-asserted-by":"publisher","award":["202204c06020009"],"award-info":[{"award-number":["202204c06020009"]}],"id":[{"id":"10.13039\/100016073","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","award":["2008085QC138, 2008085MC91"],"award-info":[{"award-number":["2008085QC138, 2008085MC91"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>The high mortality rate of weaned piglets infected with porcine epidemic diarrhea virus (PEDV) poses a serious threat to the pig industry worldwide, demanding urgent research efforts related to developing effective antiviral drugs to prevent and treat PEDV infection. Small molecules can possibly prevent the spread of infection by targeting specific vital components of the pathogen\u2019s genome. Main protease (Mpro, also named 3CL protease) plays essential roles in PEDV replication and has emerged as a promising target for the inhibition of PEDV. In this study, wogonin exhibited antiviral activity against a PEDV variant isolate, interacting with the PEDV particles and inhibiting the internalization, replication and release of PEDV. The molecular docking model indicated that wogonin was firmly embedded in the groove of the active pocket of Mpro. Furthermore, the interaction between wogonin and Mpro was validated in silico <jats:italic>via<\/jats:italic> microscale thermophoresis and surface plasmon resonance analyses. In addition, the results of a fluorescence resonance energy transfer (FRET) assay indicated that wogonin exerted an inhibitory effect on Mpro. These findings provide useful insights into the antiviral activities of wogonin, which could support future research into anti-PEDV drugs.`<\/jats:p>","DOI":"10.3389\/fcimb.2023.1123650","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T05:57:10Z","timestamp":1678859830000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["In silico and in vitro evaluation of antiviral activity of wogonin against main protease of porcine epidemic diarrhea virus"],"prefix":"10.3389","volume":"13","author":[{"given":"Jieru","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehuai","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fazhi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaocheng","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1126\/science.1085658","article-title":"Coronavirus main proteinase (3CLpro) structure: Basis for design of anti-SARS drugs","volume":"300","author":"Anand","year":"2003","journal-title":"Science"},{"key":"B2","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1089\/jir.2008.0125","article-title":"Production of cytokines and stimulation of resistance to viral infection in human leukocytes by scutellaria baicalensis flavones","volume":"28","author":"Blach-Olszewska","year":"2008","journal-title":"J. Interferon Cytokine Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.canlet.2010.04.004","article-title":"Reactive oxygen species-mitochondria pathway involved in LYG-202-induced apoptosis in human hepatocellular carcinoma HepG(2) cells","volume":"296","author":"Chen","year":"2010","journal-title":"Cancer Lett."},{"key":"B4","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.antiviral.2008.10.002","article-title":"Antiviral activity of quercetin 7-rhamnoside against porcine epidemic diarrhea virus","volume":"81","author":"Choi","year":"2009","journal-title":"Antiviral Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1186\/s12866-020-01916-2","article-title":"Wogonin inhibits in vitro herpes simplex virus type 1 and 2 infection by modulating cellular NF-kappaB and MAPK pathways","volume":"20","author":"Chu","year":"2020","journal-title":"BMC Microbiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1126\/science.abb4489","article-title":"Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease","volume":"368","author":"Dai","year":"2020","journal-title":"Science"},{"key":"B7","doi-asserted-by":"publisher","first-page":"7818","DOI":"10.1021\/acs.jmedchem.2c00224","article-title":"Structure-guided design of potent spirocyclic inhibitors of severe acute respiratory syndrome coronavirus-2 3C-like protease","volume":"65","author":"Dampalla","year":"2022","journal-title":"J. Med. Chem."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2961","DOI":"10.3390\/ijms21082961","article-title":"Glycyrrhizin inhibits PEDV infection and proinflammatory cytokine secretion via the HMGB1\/TLR4-MAPK p38 pathway","volume":"21","author":"Gao","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"52","DOI":"10.7748\/ns2014.04.28.33.52.e8249","article-title":"Varicella zoster virus: chickenpox and shingles","volume":"28","author":"Gould","year":"2014","journal-title":"Nurs. Stand"},{"key":"B10","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.virusres.2007.02.015","article-title":"Evaluating the 3C-like protease activity of SARS-coronavirus: Recommendations for standardized assays for drug discovery","volume":"133","author":"Grum-Tokars","year":"2008","journal-title":"Virus Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.antiviral.2007.01.002","article-title":"Anti-hepatitis b virus activity of wogonin in vitro and in vivo","volume":"74","author":"Guo","year":"2007","journal-title":"Antiviral Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"813","DOI":"10.4268\/cjcmm20160509","article-title":"Research progress of anti-drug resistance in traditional Chinese medicine","volume":"41","author":"Han","year":"2016","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"B13","doi-asserted-by":"publisher","first-page":"31257","DOI":"10.1074\/jbc.M502577200","article-title":"Mechanism of the maturation process of SARS-CoV 3CL protease","volume":"280","author":"Hsu","year":"2005","journal-title":"J. Biol. Chem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"9779","DOI":"10.1007\/s11033-020-05972-9","article-title":"Potential therapeutic and pharmacological effects of wogonin: An updated review","volume":"47","author":"Huynh","year":"2020","journal-title":"Mol. Biol. Rep."},{"key":"B15","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/S1875-5364(17)30005-5","article-title":"Anti-tumor activity of wogonin, an extract from scutellaria baicalensis, through regulating different signaling pathways","volume":"15","author":"Huynh","year":"2017","journal-title":"Chin. J. Nat. Med."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05514-2","article-title":"Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir","volume":"613","author":"Iketani","year":"2022","journal-title":"Nature"},{"key":"B17","doi-asserted-by":"publisher","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":"B18","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1007\/s10565-013-9251-4","article-title":"Wogonin induces apoptosis by suppressing E6 and E7 expressions and activating intrinsic signaling pathways in HPV-16 cervical cancer cells","volume":"29","author":"Kim","year":"2013","journal-title":"Cell Biol. Toxicol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"8095","DOI":"10.3390\/ijms21218095","article-title":"Inhibition of porcine epidemic diarrhea virus replication and viral 3C-like protease by quercetin","volume":"21","author":"Li","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"402","DOI":"10.3390\/v14020402","article-title":"Ergosterol peroxide inhibits porcine epidemic diarrhea virus infection in vero cells by suppressing ROS generation and p53 activation","volume":"14","author":"Liu","year":"2022","journal-title":"Viruses"},{"key":"B21","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.ctrv.2008.09.005","article-title":"New therapeutic aspects of flavones: the anticancer properties of scutellaria and its main active constituents wogonin, baicalein and baicalin","volume":"35","author":"Li-Weber","year":"2009","journal-title":"Cancer Treat Rev."},{"key":"B22","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/s0378-8741(01)00389-0","article-title":"Antiviral Chinese medicinal herbs against respiratory syncytial virus","volume":"79","author":"Ma","year":"2002","journal-title":"J. Ethnopharmacol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"942","DOI":"10.2174\/1389450116666150416120559","article-title":"AMP-activated protein kinase as a target for pathogens: Friends or foes","volume":"17","author":"Moreira","year":"2016","journal-title":"Curr. Drug Targets"},{"key":"B24","doi-asserted-by":"publisher","first-page":"4138","DOI":"10.1016\/j.bmc.2008.01.011","article-title":"Structure-based virtual screening against SARS-3CL(pro) to identify novel non-peptidic hits","volume":"16","author":"Mukherjee","year":"2008","journal-title":"Bioorg Med. Chem."},{"key":"B25","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.phrs.2017.12.034","article-title":"Targeting oncogenic transcription factors by polyphenols: A novel approach for cancer therapy","volume":"130","author":"Rajagopal","year":"2018","journal-title":"Pharmacol. Res."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111310","article-title":"Research progress of traditional Chinese medicine against COVID-19","volume":"137","author":"Ren","year":"2021","journal-title":"BioMed. Pharmacother."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.856711","article-title":"Inhibition of porcine epidemic diarrhea virus by cinchonine via inducing cellular autophagy","volume":"12","author":"Ren","year":"2022","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"375","DOI":"10.3390\/biomedicines9040375","article-title":"Rutin is a low micromolar inhibitor of SARS-CoV-2 main protease 3CLpro: Implications for drug design of quercetin analogs","volume":"9","author":"Rizzuti","year":"2021","journal-title":"Biomedicines"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2020.128933","article-title":"An in-silico evaluation of different bioactive molecules of tea for their inhibition potency against non structural protein-15 of SARS-CoV-2","volume":"346","author":"Sharma","year":"2021","journal-title":"Food Chem."},{"key":"B30","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/s43018-021-00279-5","article-title":"Small-molecule inhibitors that disrupt the MTDH-SND1 complex suppress breast cancer progression and metastasis","volume":"3","author":"Shen","year":"2022","journal-title":"Nat. Cancer"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2020.104378","article-title":"Porcine epidemic diarrhea virus infection blocks cell cycle and induces apoptosis in pig intestinal epithelial cells","volume":"147","author":"Shen","year":"2020","journal-title":"Microb. Pathog."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.1020286","article-title":"The add-on effect of shufeng jiedu capsule for treating COVID-19: A systematic review and meta-analysis","volume":"9","author":"Sheng","year":"2022","journal-title":"Front. Med. (Lausanne)"},{"key":"B33","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1021\/acs.jpclett.6b02894","article-title":"Extraction of thermodynamic parameters of protein unfolding using parallelized differential scanning fluorimetry","volume":"8","author":"Wright","year":"2017","journal-title":"J. Phys. Chem. Lett."},{"key":"B34","doi-asserted-by":"publisher","first-page":"6552","DOI":"10.1038\/s41598-021-85880-5","article-title":"Puerarin enhances intestinal function in piglets infected with porcine epidemic diarrhea virus","volume":"11","author":"Wu","year":"2021","journal-title":"Sci. Rep."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00169","article-title":"Quantitative proteomic analysis reveals antiviral and anti-inflammatory effects of puerarin in piglets infected with porcine epidemic diarrhea virus","volume":"11","author":"Wu","year":"2020","journal-title":"Front. Immunol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.bcp.2014.09.008","article-title":"Wogonin reverses multi-drug resistance of human myelogenous leukemia K562\/A02 cells via downregulation of MRP1 expression by inhibiting Nrf2\/ARE signaling pathway","volume":"92","author":"Xu","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"4971","DOI":"10.1021\/jm0603926","article-title":"Synthesis, crystal structure, structure-activity relationships, and antiviral activity of a potent SARS coronavirus 3CL protease inhibitor","volume":"49","author":"Yang","year":"2006","journal-title":"J. Med. Chem."},{"key":"B38","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.virol.2016.04.018","article-title":"Structural basis for the dimerization and substrate recognition specificity of porcine epidemic diarrhea virus 3C-like protease","volume":"494","author":"Ye","year":"2016","journal-title":"Virology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"24","DOI":"10.3390\/v12020240","article-title":"Structural basis for inhibiting porcine epidemic diarrhea virus replication with the 3C-like protease inhibitor GC376","volume":"12","author":"Ye","year":"2020","journal-title":"Viruses"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.jmb.2007.06.001","article-title":"A mechanistic view of enzyme inhibition and peptide hydrolysis in the active site of the SARS-CoV 3C-like peptidase","volume":"371","author":"Yin","year":"2007","journal-title":"J. Mol. Biol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"258","DOI":"10.3390\/v14020258","article-title":"Levistolide a inhibits PEDV replication via inducing ROS generation","volume":"14","author":"Zeng","year":"2022","journal-title":"Viruses"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008682","article-title":"Transferrin receptor 1 levels at the cell surface influence the susceptibility of newborn piglets to PEDV infection","volume":"16","author":"Zhang","year":"2020","journal-title":"PloS Pathog."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.797476","article-title":"Monolaurin confers a protective effect against porcine epidemic diarrhea virus infection in piglets by regulating the interferon pathway","volume":"12","author":"Zhang","year":"2021","journal-title":"Front. Immunol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.yrtph.2011.03.008","article-title":"Developmental toxicity and genotoxicity studies of wogonin","volume":"60","author":"Zhao","year":"2011","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.ejphar.2014.05.011","article-title":"Wogonin inhibits LPS-induced tumor angiogenesis via suppressing PI3K\/Akt\/NF-kappaB signaling","volume":"737","author":"Zhao","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2019.112876","article-title":"Exploring the effective materials of flavonoids-enriched extract from scutellaria baicalensis roots based on the metabolic activation in influenza a virus induced acute lung injury","volume":"177","author":"Zhi","year":"2020","journal-title":"J. Pharm. BioMed. Anal."},{"key":"B47","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.phymed.2018.12.009","article-title":"In vivo effect of quantified flavonoids-enriched extract of scutellaria baicalensis root on acute lung injury induced by influenza a virus","volume":"57","author":"Zhi","year":"2019","journal-title":"Phytomedicine"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1007\/s12250-021-00415-6","article-title":"Two inhibitors against the 3C-like proteases of swine coronavirus and feline coronavirus","volume":"36","author":"Zhou","year":"2021","journal-title":"Virol. Sin."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1123650\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T05:57:15Z","timestamp":1678859835000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1123650\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,15]]},"references-count":48,"alternative-id":["10.3389\/fcimb.2023.1123650"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2023.1123650","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,15]]},"article-number":"1123650"}}