{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:39:36Z","timestamp":1792143576677,"version":"4.4.0"},"reference-count":42,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T00:00:00Z","timestamp":1589932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002631","name":"Gachon University","doi-asserted-by":"publisher","award":["GCU-2019-0703"],"award-info":[{"award-number":["GCU-2019-0703"]}],"id":[{"id":"10.13039\/501100002631","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Research Foundation (NRF) funded by the Ministry of Education in Korea","award":["2018R1A6A3A03012203"],"award-info":[{"award-number":["2018R1A6A3A03012203"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>We previously reported that the ethyl acetate (EtOAc) fraction of a 70% ethanol extract of Elaeocarpus sylvestris (ESE) inhibits varicella-zoster virus (VZV) and human cytomegalovirus (HCMV) replication in vitro. PGG (1,2,3,4,6-penta-O-galloyl-\u00df-D-glucose) is a major chemical constituent of the EtOAc fraction of ESE that inhibits VZV but not HCMV replication. In this study, we comprehensively screened the chemical compounds identified in the EtOAc fraction of ESE for potential antiviral properties. Among the examined compounds, quercetin and isoquercitrin displayed potent antiviral activities against both VZV and HCMV with no significant cytotoxic effects. Both compounds strongly suppressed the expression of VZV and HCMV immediate\u2013early (IE) genes. Our collective results indicated that, in addition to PGG, quercetin and isoquercitrin are bioactive compounds in the EtOAc fraction of ESE that effectively inhibit human herpesvirus replication.<\/jats:p>","DOI":"10.3390\/molecules25102379","type":"journal-article","created":{"date-parts":[[2020,5,22]],"date-time":"2020-05-22T10:18:18Z","timestamp":1590142698000},"page":"2379","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Antiviral Activities of Quercetin and Isoquercitrin Against Human Herpesviruses"],"prefix":"10.3390","volume":"25","author":[{"given":"Chae Hyun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Life Science, Gachon University, Seongnam-Si, Gyeonggi-Do 13120, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Life Science, Gachon University, Seongnam-Si, Gyeonggi-Do 13120, Korea"},{"name":"Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7900-5012","authenticated-orcid":false,"given":"Yoon-Jae","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Life Science, Gachon University, Seongnam-Si, Gyeonggi-Do 13120, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/0147-9571(91)90122-T","article-title":"The diversity and unity of herpesviridae","volume":"14","author":"Roizman","year":"1991","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1093\/emboj\/cdg086","article-title":"Structure of the herpesvirus major capsid protein","volume":"22","author":"Bowman","year":"2003","journal-title":"EMBO J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.vetmic.2010.02.014","article-title":"Herpesvirus systematics","volume":"143","author":"Davison","year":"2010","journal-title":"Veter- Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Bae, S., Kang, S.C., and Song, Y.-J. (2017). Inhibition of human cytomegalovirus immediate-early gene expression and replication by the ethyl acetate (EtOAc) fraction of Elaeocarpus sylvestris in vitro. BMC Complement. Altern. Med., 17.","DOI":"10.1186\/s12906-017-1941-7"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.antiviral.2017.06.018","article-title":"1,2,3,4,6-Penta-O-galloyl-\u00df-D-glucose, a bioactive compound in Elaeocarpus sylvestris extract, inhibits varicella-zoster virus replication","volume":"144","author":"Bae","year":"2017","journal-title":"Antivir. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.foodchem.2008.12.020","article-title":"Antioxidant properties of 1,2,3,4,6-penta-O-galloyl-beta-D-glucose from Elaeocarpus sylvestris var. ellipticus","volume":"115","author":"Piao","year":"2009","journal-title":"Food Chem."},{"key":"ref_7","unstructured":"Moffat, J., Ku, C.-C., Zerboni, L., and Sommer, M. (2010). VZV: Pathogenesis and the disease consequences of primary infection. Human Herpesviruses, Cambridge University Press."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3904","DOI":"10.1128\/JVI.02137-08","article-title":"The Replication Cycle of Varicella-Zoster Virus: Analysis of the Kinetics of Viral Protein Expression, Genome Synthesis, and Virion Assembly at the Single-Cell Level","volume":"83","author":"Reichelt","year":"2009","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/path.4437","article-title":"The pathogenesis of human cytomegalovirus","volume":"235","author":"Griffiths","year":"2014","journal-title":"J. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1128\/CMR.00034-08","article-title":"Immunobiology of Human Cytomegalovirus: From Bench to Bedside","volume":"22","author":"Crough","year":"2009","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_11","first-page":"3347","article-title":"Human cytomegalovirus infection and expression in human malignant glioma","volume":"62","author":"Cobbs","year":"2002","journal-title":"Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S1386-6532(02)00188-9","article-title":"Human cytomegalovirus load in various body fluids of congenitally infected newborns","volume":"25","author":"Genser","year":"2002","journal-title":"J. Clin. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1099\/vir.0.81891-0","article-title":"Latency and reactivation of human cytomegalovirus","volume":"87","author":"Sinclair","year":"2006","journal-title":"J. Gen. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jcv.2004.02.009","article-title":"Antiviral drugs in current clinical use","volume":"30","year":"2004","journal-title":"J. Clin. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/358160a0","article-title":"Human cytomegalovirus UL97 open reading frame encodes a protein that phosphorylates the antiviral nucleoside analogue ganciclovir","volume":"358","author":"Littler","year":"1992","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2010\/602783","article-title":"Acyclovir Nephrotoxicity: A Case Report Highlighting the Importance of Prevention, Detection, and Treatment of Acyclovir-Induced Nephropathy","volume":"2010","author":"Fleischer","year":"2010","journal-title":"Case Rep. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.trsl.2011.07.002","article-title":"Acyclovir-induced nephrotoxicity: The role of the acyclovir aldehyde metabolite","volume":"158","author":"Gunness","year":"2011","journal-title":"Transl. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1136\/adc.70.2.133","article-title":"Acyclovir resistant varicella zoster and HIV infection","volume":"70","author":"Lyall","year":"1994","journal-title":"Arch. Dis. Child."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1038\/sj.gt.3301779","article-title":"Pronounced cytostatic activity and bystander effect of a novel series of fluorescent tricyclic acyclovir and ganciclovir derivatives in herpes simplex virus thymidine kinase gene-transduced tumor cell lines","volume":"9","author":"Balzarini","year":"2002","journal-title":"Gene Ther."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Li, Y., Yao, J., Han, C., Yang, J., Chaudhry, M.T., Wang, S., Liu, H., and Yin, Y. (2016). Quercetin, Inflammation and Immunity. Nutrients, 8.","DOI":"10.3390\/nu8030167"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Arvin, A., Campadelli-Fiume, G., Mocarski, E., Moore, P.S., Roizman, B., Whitley, R., and Yamanishi, K. (2007). Antiviral therapy of varicella-zoster virus infections. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis, Cambridge University Press.","DOI":"10.1017\/CBO9780511545313"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1128\/JCM.36.4.958-964.1998","article-title":"Flow Cytometric Determination of Ganciclovir Susceptibilities of Human Cytomegalovirus Clinical Isolates","volume":"36","author":"McSharry","year":"1998","journal-title":"J. Clin. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1212\/01.wnl.0000438228.48470.86","article-title":"Varicella-zoster virus trigeminal ganglioneuritis without rash","volume":"82","author":"Birlea","year":"2013","journal-title":"Neurol."},{"key":"ref_24","unstructured":"Mocarski, E.S., Shenk, T., Griffiths, P.D., and Pass, R.F. (2013). Cytomegaloviruses, Wolters Kluwer Health. [6th ed.]."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"84","DOI":"10.4103\/0973-7847.194044","article-title":"Overviews of biological importance of quercetin: A bioactive flavonoid","volume":"10","author":"Parasuraman","year":"2016","journal-title":"Pharmacogn. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.fct.2014.03.018","article-title":"Isoquercitrin: Pharmacology, toxicology, and metabolism","volume":"68","author":"Vrba","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.antiviral.2012.09.010","article-title":"Eight flavonoids and their potential as inhibitors of human cytomegalovirus replication","volume":"96","author":"Cotin","year":"2012","journal-title":"Antivir. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1017\/S000711451000053X","article-title":"Oral bioavailability of quercetin from different quercetin glycosides in dogs","volume":"104","author":"Reinboth","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.antiviral.2011.09.005","article-title":"Houttuynia cordata blocks HSV infection through inhibition of NF-kappaB activation","volume":"92","author":"Chen","year":"2011","journal-title":"Antiviral Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1093\/jac\/dkg291","article-title":"In vitro antiviral activities of Caesalpinia pulcherrima and its related flavonoids","volume":"52","author":"Chiang","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hung, P.-Y., Ho, B.-C., Lee, S.-Y., Chang, S.-Y., Kao, C.-L., Lee, S.-S., and Lee, C.-N. (2015). Houttuynia cordata Targets the Beginning Stage of Herpes Simplex Virus Infection. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0115475"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1002\/jmv.1890150110","article-title":"Antiviral effect of flavonoids on human viruses","volume":"15","author":"Kaul","year":"1985","journal-title":"J. Med Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s12272-017-0898-x","article-title":"The anti-HSV-1 effect of quercetin is dependent on the suppression of TLR-3 in Raw 264.7 cells","volume":"40","author":"Lee","year":"2017","journal-title":"Arch. Pharmacal Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1007\/BF02978215","article-title":"Antiherpetic activities of flavonoids against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2)in vitro","volume":"28","author":"Lyu","year":"2005","journal-title":"Arch. Pharmacal Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1128\/JVI.05746-11","article-title":"The Human Cytomegalovirus Protein TRS1 Inhibits Autophagy via Its Interaction with Beclin 1","volume":"86","author":"Chaumorcel","year":"2011","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1128\/JVI.01470-06","article-title":"Varicella-Zoster Virus Infection of Human Fibroblast Cells Activates the c-Jun N-Terminal Kinase Pathway","volume":"81","author":"Zapata","year":"2006","journal-title":"J. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"840","DOI":"10.3892\/or.2014.3626","article-title":"Isoquercitrin inhibits the progression of pancreatic cancer in vivo and in vitro by regulating opioid receptors and the mitogen-activated protein kinase signalling pathway","volume":"33","author":"Chen","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.bbrc.2006.05.198","article-title":"The flavonoid quercetin induces apoptosis and inhibits JNK activation in intimal vascular smooth muscle cells","volume":"346","author":"Lodi","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.virol.2016.06.017","article-title":"Analysis of single nucleotide polymorphism among Varicella-Zoster Virus and identification of vaccine-specific sites","volume":"496","author":"Jeon","year":"2016","journal-title":"Virology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1128\/jvi.23.3.751-767.1977","article-title":"Synthesis of Proteins and Glycoproteins in Cells Infected with Human Cytomegalovirus","volume":"23","author":"Stinski","year":"1977","journal-title":"J. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1128\/MCB.00912-13","article-title":"Role of Ca2+\/calmodulin-dependent kinase II-IRAK1 interaction in LMP1-induced NF-kappaB activation","volume":"34","author":"Kim","year":"2014","journal-title":"Mol. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1007\/s12275-015-5455-z","article-title":"Characterization of the rapamycin-inducible EBV LMP1 activation system","volume":"53","author":"Kim","year":"2015","journal-title":"J. Microbiol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/10\/2379\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:30:54Z","timestamp":1760175054000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/10\/2379"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,20]]},"references-count":42,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["molecules25102379"],"URL":"https:\/\/doi.org\/10.3390\/molecules25102379","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,20]]}}}