{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:10:25Z","timestamp":1790914225928,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Porcine epidemic diarrhea (PED) remains a persistent threat to global swine production, necessitating urgent development of targeted interventions. Our previous research established that Hypericum japonicum Thunb. ex Murray (HJT) extract exhibited significant anti-porcine epidemic diarrhea virus (PEDV) activity both in vivo and in vitro. Nevertheless, the principal bioactive constituents mediating this antiviral activity remained uncharacterized. In this study, it was demonstrated that ethanol eluates with 20% (v\/v) and 60% (v\/v) ethanol exhibited activity against PEDV. Phytochemical characterization revealed 66 distinct compounds, including 36 flavonoids and 13 organic acids identified as possible antiviral constituents. Among these, taxifolin-7-O-rhamnoside and quercetin-7-rhamnoside were identified as the most potent anti-PEDV components. Notably, neither compound exhibited significant antiviral efficacy as monotherapy. However, co-administration produced a reduction in PEDV-G2 titers. This study mechanistically links taxifolin-7-O-rhamnoside and quercetin-7-rhamnoside as core anti-PEDV phytochemicals in HJT extract. These findings support the further development of HJT as a potential therapeutic for PED.<\/jats:p>","DOI":"10.3390\/v17070900","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T07:55:43Z","timestamp":1751442943000},"page":"900","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Screening of Active Compounds Against Porcine Epidemic Diarrhea Virus in Hypericum japonicum Thunb. ex Murray Extracts"],"prefix":"10.3390","volume":"17","author":[{"given":"Hongyu","family":"Rao","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Plant Stress Biology, State Key Laboratory of Biocontrol, Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-Evaluation of Post Marketed TCM, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Plant Stress Biology, State Key Laboratory of Biocontrol, Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-Evaluation of Post Marketed TCM, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Plant Stress Biology, State Key Laboratory of Biocontrol, Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-Evaluation of Post Marketed TCM, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlong","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Plant Stress Biology, State Key Laboratory of Biocontrol, Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-Evaluation of Post Marketed TCM, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyue","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Plant Stress Biology, State Key Laboratory of Biocontrol, Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-Evaluation of Post Marketed TCM, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Su","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Plant Stress Biology, State Key Laboratory of Biocontrol, Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-Evaluation of Post Marketed TCM, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peibo","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Plant Stress Biology, State Key Laboratory of Biocontrol, Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-Evaluation of Post Marketed TCM, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e01896-17","DOI":"10.1128\/JVI.01896-17","article-title":"Structural Basis for the Inhibition of Host Gene Expression by Porcine Epidemic Diarrhea Virus Nsp1","volume":"92","author":"Shen","year":"2018","journal-title":"J. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1080\/15548627.2023.2181615","article-title":"N Protein of PEDV Plays Chess Game with Host Proteins by Selective Autophagy","volume":"19","author":"Zhai","year":"2023","journal-title":"Autophagy"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"198045","DOI":"10.1016\/j.virusres.2020.198045","article-title":"Porcine Epidemic Diarrhea Virus (PEDV): An Update on Etiology, Transmission, Pathogenesis, and Prevention and Control","volume":"286","author":"Jung","year":"2020","journal-title":"Virus Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Chen, Y., Zhou, J., Wang, X., Ma, L., Li, J., Yang, L., Yuan, H., Pang, D., and Ouyang, H. (2022). Porcine Epidemic Diarrhea Virus: An Updated Overview of Virus Epidemiology, Virulence Variation Patterns and Virus\u2013Host Interactions. Viruses, 14.","DOI":"10.3390\/v14112434"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lei, J., Miao, Y., Bi, W., Xiang, C., Li, W., Zhang, R., Li, Q., and Yang, Z. (2024). Porcine Epidemic Diarrhea Virus: Etiology, Epidemiology, Antigenicity, and Control Strategies in China. Animals, 14.","DOI":"10.3390\/ani14020294"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"106185","DOI":"10.1016\/j.micpath.2023.106185","article-title":"Insights and Progress on Epidemic Characteristics, Genotyping, and Preventive Measures of PEDV in China: A Review","volume":"181","author":"Li","year":"2023","journal-title":"Microb. Pathog."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1186\/s12985-015-0421-2","article-title":"Porcine Epidemic Diarrhea Virus: An Emerging and Re-Emerging Epizootic Swine Virus","volume":"12","author":"Lee","year":"2015","journal-title":"Virol. J."},{"key":"ref_8","unstructured":"(2024, December 16). August-GSDMR-Report-8-6-2024.Pdf. Available online: https:\/\/www.swinehealth.org\/global-disease-surveillance-reports\/."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s40813-022-00268-9","article-title":"Growing Pig Incidence Rate, Control and Prevention of Porcine Epidemic Diarrhea Virus in a Large Pig Production System in the United States","volume":"8","author":"Kikuti","year":"2022","journal-title":"Porc. Health Manag."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.micpath.2019.01.017","article-title":"Epidemiology of Porcine Epidemic Diarrhea Virus among Chinese Pig Populations: A Meta-Analysis","volume":"129","author":"Chen","year":"2019","journal-title":"Microb. Pathog."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10733","DOI":"10.3390\/molecules190810733","article-title":"Hypericum Japonicum Thunb. Ex Murray: Phytochemistry, Pharmacology, Quality Control and Pharmacokinetics of an Important Herbal Medicine","volume":"19","author":"Liu","year":"2014","journal-title":"Molecules"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Du, H., Zhang, S., Song, M., Wang, Y., Zeng, L., Chen, Y., Xiong, W., Yang, J., Yao, F., and Wu, Y. (2016). Assessment of a Flavone-Polysaccharide Based Prescription for Treating Duck Virus Hepatitis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146046"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"03002","DOI":"10.1051\/matecconf\/20166003002","article-title":"Study on the Chemical Constituents and Anti-HBV Activity of Hypericum Japonica","volume":"60","author":"Chen","year":"2016","journal-title":"MATEC Web Conf."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1021\/acs.orglett.6b00906","article-title":"Filicinic Acid Based Meroterpenoids with Anti-Epstein\u2013Barr Virus Activities from Hypericum Japonicum","volume":"18","author":"Hu","year":"2016","journal-title":"Org. Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1021\/acs.jnatprod.5b01119","article-title":"(\u00b1)-Japonicols A\u2013D, Acylphloroglucinol-Based Meroterpenoid Enantiomers with Anti-KSHV Activities from Hypericum Japonicum","volume":"79","author":"Hu","year":"2016","journal-title":"J. Nat. Prod."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Rao, H., Su, W., Zhang, X., Wang, Y., Li, T., Li, J., Zeng, X., and Li, P. (2023). Hypericum Japonicum Extract Inhibited Porcine Epidemic Diarrhea Virus in Vitro and in Vivo. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1112610"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"118428","DOI":"10.1016\/j.jep.2024.118428","article-title":"Lizhong Decoction Inhibits Porcine Epidemic Diarrhea Virus in Vitro and in Vivo","volume":"333","author":"Chen","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","article-title":"A Simple Method of Estimating Fifty per Cent Endpoints12","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Epidemiol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zeng, X., Su, W., Zheng, Y., Liu, H., Li, P., Zhang, W., Liang, Y., Bai, Y., Peng, W., and Yao, H. (2018). UFLC-Q-TOF-MS\/MS-Based Screening and Identification of Flavonoids and Derived Metabolites in Human Urine after Oral Administration of Exocarpium Citri Grandis Extract. Molecules, 23.","DOI":"10.3390\/molecules23040895"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Cao, Y., Zhang, S., Huang, Y., Zhang, S., Wang, H., and Bao, W. (2022). The Aqueous Leaf Extract of M. Oleifera Inhibits PEDV Replication through Suppressing Oxidative Stress-Mediated Apoptosis. Animals, 12.","DOI":"10.3390\/ani12040458"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Maikhunthod, B., Chaipayang, S., Jittmittraphap, A., Thippornchai, N., Boonchuen, P., Tittabutr, P., Eumkeb, G., Sabuakham, S., Rungrotmongkol, T., and Mahalapbutr, P. (2024). Exploring the Therapeutic Potential of Thai Medicinal Plants: In Vitro Screening and in Silico Docking of Phytoconstituents for Novel Anti-SARS-CoV-2 Agents. BMC Complement. Med. Ther., 24.","DOI":"10.1186\/s12906-024-04586-z"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1002\/rmv.483","article-title":"Mechanisms of Action of Ribavirin against Distinct Viruses","volume":"16","author":"Graci","year":"2006","journal-title":"Rev. Med. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Menis Candela, F., Soria, E.A., Moliva, M.V., Su\u00e1rez Perrone, A., Reinoso, E.B., Giordano, W., and Sabini, M.C. (2024). Anti-DENV-2 Activity of Ethanolic Extracts from Arachis Hypogaea L.: Peanut Skin as a Relevant Resource of Bioactive Compounds against Dengue Virus. Plants, 13.","DOI":"10.3390\/plants13202881"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"109205","DOI":"10.1016\/j.carres.2024.109205","article-title":"Anti-Virus Activity and Mechanisms of Natural Polysaccharides from Medicinal Herbs","volume":"542","author":"Huang","year":"2024","journal-title":"Carbohydr. Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Qiao, W.-T., Yao, X., Lu, W.-H., Zhang, Y.-Q., Malhi, K.K., Li, H.-X., and Li, J.-L. (2024). Matrine Exhibits Antiviral Activities against PEDV by Directly Targeting Spike Protein of the Virus and Inducing Apoptosis via the MAPK Signaling Pathway. Int. J. Biol. Macromol., 270.","DOI":"10.1016\/j.ijbiomac.2024.132408"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Wang, J., Zeng, X., Yin, D., Yin, L., Shen, X., Xu, F., Dai, Y., and Pan, X. (2023). In Silico and in Vitro Evaluation of Antiviral Activity of Wogonin against Main Protease of Porcine Epidemic Diarrhea Virus. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1123650"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/s13567-020-00865-y","article-title":"Tomatidine Inhibits Porcine Epidemic Diarrhea Virus Replication by Targeting 3CL Protease","volume":"51","author":"Wang","year":"2020","journal-title":"Vet. Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Gong, M., Xia, X., Chen, D., Ren, Y., Liu, Y., Xiang, H., Li, X., Zhi, Y., and Mo, Y. (2023). Antiviral Activity of Chrysin and Naringenin against Porcine Epidemic Diarrhea Virus Infection. Front. Vet. Sci., 10.","DOI":"10.3389\/fvets.2023.1278997"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"He, C., Zhang, R., Yang, L., and Xiang, B. (2024). Andrographolide Inhibits Porcine Epidemic Diarrhea Virus by Inhibiting the JAK2-STAT3 Pathway and Promoting Apoptosis. Vet. Microbiol., 298.","DOI":"10.1016\/j.vetmic.2024.110235"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Sun, P., Wang, M., Li, J., Qiu, Y., Li, H., Lv, M., Bo, Z., Shen, H., and Li, L. (2022). Inhibitory Effect of Buddlejasaponin IVb on Porcine Epidemic Diarrhea Virus in Vivo and in Vitro. Vet. Microbiol., 272.","DOI":"10.1016\/j.vetmic.2022.109516"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Song, Z., Deng, C., Chen, Q., Zhao, S., Li, P., Wu, T., Hou, Y., and Yi, D. (2024). Protective Effects and Mechanisms of Ellagic Acid on Intestinal Injury in Piglets Infected with Porcine Epidemic Diarrhea Virus. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1323866"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"115311","DOI":"10.1016\/j.ejmech.2023.115311","article-title":"Broad-Spectrum Coronavirus 3C-like Protease Peptidomimetic Inhibitors Effectively Block SARS-CoV-2 Replication in Cells: Design, Synthesis, Biological Evaluation, and X-Ray Structure Determination","volume":"253","author":"Stefanelli","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Fu, X., Xu, W., Yang, Y., Li, D., Shi, W., Li, X., Chen, N., Lv, Q., Shi, Y., and Xu, J. (2025). Diverse Strategies Utilized by Coronaviruses to Evade Antiviral Responses and Suppress Pyroptosis. Int. J. Biol. Macromol., 296.","DOI":"10.1016\/j.ijbiomac.2025.139743"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Pathak, R.K., Kim, W.-I., and Kim, J.-M. (2023). Targeting the PEDV 3CL Protease for Identification of Small Molecule Inhibitors: An Insight from Virtual Screening, ADMET Prediction, Molecular Dynamics, Free Energy Landscape, and Binding Energy Calculations. J. Biol. Eng., 17.","DOI":"10.1186\/s13036-023-00342-y"},{"key":"ref_35","doi-asserted-by":"crossref","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":"2008","journal-title":"Antiviral Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1186\/1743-422X-8-460","article-title":"Quercetin 7-Rhamnoside Reduces Porcine Epidemic Diarrhea Virus Replication via Independent Pathway of Viral Induced Reactive Oxygen Species","volume":"8","author":"Song","year":"2011","journal-title":"Virol. J."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Flores-Ocelotl, M.R., Rosas-Murrieta, N.H., Moreno, D.A., Vallejo-Ruiz, V., Reyes-Leyva, J., Dom\u00ednguez, F., and Santos-L\u00f3pez, G. (2018). Taraxacum Officinale and Urtica Dioica Extracts Inhibit Dengue Virus Serotype 2 Replication in Vitro. BMC Complement. Altern. Med., 18.","DOI":"10.1186\/s12906-018-2163-3"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e2400607","DOI":"10.1002\/ardp.202400607","article-title":"Secondary Metabolite Profiles and anti-SARS-CoV-2 Activity of Ethanolic Extracts from Nine Genotypes of Cannabis sativa L","volume":"358","author":"Schadich","year":"2025","journal-title":"Arch. Pharm."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Jantan, I., Ahmad, W., and Bukhari, S.N.A. (2015). Plant-Derived Immunomodulators: An Insight on Their Preclinical Evaluation and Clinical Trials. Front. Plant Sci., 6.","DOI":"10.3389\/fpls.2015.00655"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1007\/s13238-020-00784-w","article-title":"Role of Gut Microbiota in Identification of Novel TCM-Derived Active Metabolites","volume":"12","author":"Lin","year":"2020","journal-title":"Protein Cell"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Yang, X., Sun, X., Zhou, F., Xiao, S., Zhong, L., Hu, S., Zhou, Z., Li, L., and Tan, Y. (2023). Protocatechuic Acid Alleviates Dextran-Sulfate-Sodium-Induced Ulcerative Colitis in Mice via the Regulation of Intestinal Flora and Ferroptosis. Molecules, 28.","DOI":"10.3390\/molecules28093775"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4777","DOI":"10.1039\/D3FO00605K","article-title":"Dietary Protocatechuic Acid Redistributes Tight Junction Proteins by Targeting Rho-Associated Protein Kinase to Improve Intestinal Barrier Function","volume":"14","author":"So","year":"2023","journal-title":"Food Funct."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"12487","DOI":"10.1021\/acs.jafc.3c00980","article-title":"Biotransformation of Rutin in In Vitro Porcine Ileal and Colonic Fermentation Models","volume":"71","author":"Ulluwishewa","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_44","first-page":"220","article-title":"Transformation of Trollioside and Isoquercetin by Human Intestinal Flora in Vitro","volume":"14","author":"Yuan","year":"2016","journal-title":"Chin. J. Nat. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1002\/ptr.7397","article-title":"Chemistry, Pharmacokinetics, Pharmacological Activities, and Toxicity of Quercitrin","volume":"36","author":"Chen","year":"2022","journal-title":"Phytother. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/ptr.8027","article-title":"Quercetin Ameliorates Ulcerative Colitis by Activating Aryl Hydrocarbon Receptor to Improve Intestinal Barrier Integrity","volume":"38","author":"Wang","year":"2024","journal-title":"Phytother. Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Liu, G., Fang, Y., Zhang, Y., and Zhu, M. (2024). Dihydroquercetin Improves the Proliferation of Porcine Intestinal Epithelial Cells via the Wnt\/\u03b2-Catenin Pathway. Biochem. Biophys. Res. Commun., 734.","DOI":"10.1016\/j.bbrc.2024.150460"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/7\/900\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:59:00Z","timestamp":1760032740000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/7\/900"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,26]]},"references-count":47,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["v17070900"],"URL":"https:\/\/doi.org\/10.3390\/v17070900","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,26]]}}}