{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:39:32Z","timestamp":1760236772803,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T00:00:00Z","timestamp":1639872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004396","name":"Thailand Research Fund","doi-asserted-by":"publisher","award":["PHD58I0064"],"award-info":[{"award-number":["PHD58I0064"]}],"id":[{"id":"10.13039\/501100004396","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Herpes simplex virus (HSV) infections are prevalent worldwide and are the cause of life- threatening diseases. Standard treatment with antiviral drugs, such as acyclovir, could prevent serious complications; however, resistance has been reported specifically among immunocompromised patients. Therefore, the development of an alternative approach is needed. The silk cocoon derived from silkworm, Bombyx mori, has been recognized for its broad-spectrum biological activity, including antiviral activity; however, its effects against HSV infection are unknown. In this study, we investigated the inhibitory effects of silk extracts derived from the cocoon shell, silk cocoon, silkworm pupa and non-sericin extract, on blocking HSV-1 and HSV-2 binding to host cells, resulting in the inhibition of the virus infection in Vero cells. Non-sericin extract demonstrated the greatest effectiveness on inhibiting HSV-1 and HSV-2 binding activity. Moreover, the virucidal effect to inactivate HSV-1 and HSV-2 was determined and revealed that non-sericin extract also exerted the highest potential activity. Using the treatment of non-sericin extract in HSV-2-infected HeLa cells could significantly lower the HSV-induced cell death and prevent inflammation via lowering the inflammatory cytokine gene expression. The non-sericin extract was analyzed for its bioactive compounds in which gallic acid, flavonoid and xanthophyll were identified, and might have partially contributed to its antiviral activity. The finding in our study suggested the potential of silk extract as an alternative therapeutic treatment for HSV infection.<\/jats:p>","DOI":"10.3390\/antibiotics10121553","type":"journal-article","created":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T20:41:55Z","timestamp":1639946515000},"page":"1553","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Anti-Herpes Simplex Virus Efficacy of Silk Cocoon, Silkworm Pupa and Non-Sericin Extracts"],"prefix":"10.3390","volume":"10","author":[{"given":"Kanyaluck","family":"Jantakee","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6376-7116","authenticated-orcid":false,"given":"Panchika","family":"Prangkio","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3634-1881","authenticated-orcid":false,"given":"Aussara","family":"Panya","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Research Center in Bioresources for Agriculture, Industry, and Medicine, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0754-0638","authenticated-orcid":false,"given":"Yingmanee","family":"Tragoolpua","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Research Center in Bioresources for Agriculture, Industry, and Medicine, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,19]]},"reference":[{"key":"ref_1","first-page":"E27","article-title":"Epidemiology of herpes simplex virus type 1 and 2 in Italy: A seroprevalence study from 2000 to 2014","volume":"58","author":"Marchi","year":"2017","journal-title":"J. Prev. Med. Hyg."},{"key":"ref_2","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":"Vet. Microbiol."},{"key":"ref_3","first-page":"1","article-title":"Experimental dissection of the lytic replication cycles of herpes simplex viruses in vitro","volume":"9","author":"Corrales","year":"2018","journal-title":"Front Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"941","DOI":"10.3390\/v3070941","article-title":"Peripheral tissues, alphaherpesviruses and the cytoskeleton in neuronal infections","volume":"3","author":"Zaichick","year":"2011","journal-title":"Viruses"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1542\/pir.30.4.119","article-title":"Herpes Simplex","volume":"30","author":"Chayavichitsilp","year":"2009","journal-title":"Pediatr. Rev."},{"key":"ref_6","first-page":"1","article-title":"Pediatric Herpes Simplex Virus Infections: An Evidence-Based Approach to Treatment","volume":"11","author":"Sanders","year":"2014","journal-title":"Pediatr. Emerg. Med. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Smith, T.T., and Whitley, R.J. (2017). SECTION 8 Clinical Microbiology: Viruses. Infect. Dis., 1426\u20131438.","DOI":"10.1016\/B978-0-7020-6285-8.00166-0"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S1462399403006975","article-title":"Herpes simplex virus latency","volume":"5","author":"Lachmann","year":"2003","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1016\/S0140-6736(07)61908-4","article-title":"Genital herpes","volume":"370","author":"Gupta","year":"2007","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.jaad.2007.06.027","article-title":"Human herpes simplex virus infections: Epidemiology, pathogenesis, symptomatology, diagnosis, and management","volume":"57","author":"Fatahzadeh","year":"2007","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1128\/AAC.00615-10","article-title":"Resistance of herpes simplex viruses to nucleoside analogues: Mechanisms, prevalence, and management","volume":"55","author":"Piret","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"28","DOI":"10.4172\/jaa.1000060","article-title":"Antiviral drug therapy exploiting medicinal plants","volume":"5","author":"Babar","year":"2013","journal-title":"J. Antivir Antiretrovir."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.tips.2014.06.004","article-title":"New pharmacological strategies to fight enveloped viruses","volume":"35","author":"Wisskirchen","year":"2014","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kumar, D., and Kundapur, R. (2015). Chapter 3 Biomedical Applications of Silkworm Pupae Proteins. Biomedical Applications of Natural Proteins, Springer.","DOI":"10.1007\/978-81-322-2491-4"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0734-9750(02)00003-4","article-title":"Applications of natural silk protein sericin in biomaterials","volume":"20","author":"Zhang","year":"2002","journal-title":"Biotechnol. Adv."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1002\/jbm.b.32802","article-title":"Surface modification of Thai silk fibroin scaffolds with gelatin and chitooligosaccharide for enhanced osteogenic differentiation of bone marrow-derived mesenchymal stem cells","volume":"100","author":"Wongputtaraksa","year":"2012","journal-title":"J. Biomed. Mater. Res. Part B Appl. Biomater."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.msec.2015.12.082","article-title":"Processing and Characterization of Silk Sericin from Bombyx mori and Its Application in Biomaterials and Biomedicines","volume":"61","author":"Cao","year":"2016","journal-title":"Mater. Sci. Eng."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.seppur.2008.02.020","article-title":"Extraction of flavonoids and carotenoids from Thai silk waste and antioxidant activity of extracts","volume":"62","author":"Prommuak","year":"2008","journal-title":"Sep. Purif. Technol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"315","DOI":"10.2471\/BLT.19.237149","article-title":"Herpes simplex virus: Global infection prevalence and incidence estimates 2016","volume":"98","author":"James","year":"2020","journal-title":"Bull. World Health Organ."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/S0140-6736(00)04638-9","article-title":"Herpes Simplex Virus Infections","volume":"357","author":"Whitley","year":"2001","journal-title":"Lancet"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"45","DOI":"10.4067\/S0716-97602012000100006","article-title":"Effects of Silk Sericin on the Proliferation and Apoptosis of Colon Cancer Cells","volume":"45","author":"Kaewkorn","year":"2012","journal-title":"Biol. Res."},{"key":"ref_22","first-page":"2016","article-title":"Silkworm sericin: Properties and biomedical applications","volume":"14","author":"Kunz","year":"2016","journal-title":"Biomed Res. Int."},{"key":"ref_23","first-page":"1","article-title":"Extraction, Structural and Functional Properties of Silk Sericin Biopolymer from Bombyx mori Silk Cocoon Waste","volume":"9","author":"Saha","year":"2019","journal-title":"Int. J. Text. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/nsmb.1456","article-title":"Viral membrane fusion","volume":"15","author":"Harrison","year":"2008","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"13075","DOI":"10.1073\/pnas.0805862105","article-title":"Surfen, a small molecule antagonist of heparan sulfate","volume":"105","author":"Schuksz","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e01525-15","DOI":"10.1128\/mBio.01525-15","article-title":"Subassemblies and Asymmetry in Assembly of Herpes Simplex Virus Procapsid","volume":"6","author":"Aksyuk","year":"2015","journal-title":"Mbio"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3231","DOI":"10.1128\/AAC.00149-11","article-title":"Inhibition of Herpes Simplex Virus Type 1 and Type 2 Infections by Peptide-Derivatized Dendrimers","volume":"55","author":"Luganini","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.jep.2010.12.038","article-title":"Proanthocyanidin-enriched extract from Myrothamnus flabellifolia Welw. exerts antiviral activity against herpes simplex virus type 1 by inhibition of viral adsorption and penetration","volume":"134","author":"Gescher","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1472-6882-13-266","article-title":"In Vitro Anti-Herpes Simplex Virus Activity of Crude Extract of the Roots of Nauclea Latifolia Smith (Rubiaceae)","volume":"13","author":"Donalisio","year":"2013","journal-title":"BMC Complementary Altern. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11274-015-1798-1","article-title":"Anti-herpes simplex virus activity of polysaccharides from Eucheuma gelatinae","volume":"31","author":"Jin","year":"2015","journal-title":"World J. Microb. Biot."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12906-017-1620-8","article-title":"Anti-HSV-2 Activity of Terminalia Chebula Retz Extract and Its Constituents, Chebulagic and Chebulinic Acids","volume":"17","author":"Kesharwani","year":"2017","journal-title":"BMC Complementary Altern. Med."},{"key":"ref_32","first-page":"538","article-title":"Antiviralactivity of Rhus aromatic (fragrant sumac) extracts against two types of hepes simplex viruses in cell culture","volume":"64","author":"Reichling","year":"2009","journal-title":"Pharmazie"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1002\/ptr.3590","article-title":"Effects of Ilex paraguariensis A.St.Hil.(yerba mate) on herpes simplex virus type 1 and 2 replication","volume":"26","author":"Moritz","year":"2012","journal-title":"Phytother. Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zhang, X., Jia, R., Zhou, J., Wang, M., Yin, Z., and Cheng, A. (2016). Capsid-Targeted Viral Inactivation: A Novel Tactic for Inhibiting Replication in Viral Infections. Viruses, 8.","DOI":"10.3390\/v8090258"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.virusres.2016.11.002","article-title":"The interaction between human papillomavirus and other viruses","volume":"231","author":"Guidry","year":"2017","journal-title":"Virus Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"290","DOI":"10.3389\/fimmu.2019.00290","article-title":"Herpes simplex virus type 2 immediate early protein ICP27 inhibits IFN-\u03b2 production in mucosal epithelial cells by antagonizing IRF3 activation","volume":"10","author":"Guan","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0031-9422(01)00477-0","article-title":"Flavonoid 5-Glucosides from the Cocoon Shell of the Silkworm, Bombyx mori","volume":"59","author":"Tamura","year":"2002","journal-title":"Phytochemistry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1097\/MCO.0b013e32831394b8","article-title":"Quercetin: Potentials in the prevention and therapy of disease","volume":"11","author":"Bischoff","year":"2008","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1271\/bbb.64.1664","article-title":"Sulfated fibroin, a novel sulfated peptide derived from silk, inhibits human immunodeficiency virus replication in vitro","volume":"68","author":"Gotoh","year":"2000","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_40","first-page":"43","article-title":"Natural Iminosugar Derivatives of 1-Deoxynojirimycin Inhibit Glycosylation of Hepatitis Viral Envelope Proteins","volume":"45","author":"Jacob","year":"2007","journal-title":"J. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"10725","DOI":"10.1128\/JVI.77.19.10725-10729.2003","article-title":"A lipase isolated from the silkworm Bombyx mori shows antiviral activity against nucleopolyhedrovirus","volume":"77","author":"Ponnuvel","year":"2003","journal-title":"J. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1631\/jzus.B1600460","article-title":"Immune response of T cells during herpes simplex","volume":"18","author":"Zhang","year":"2017","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1039\/C1FO10148J","article-title":"Isolation and Bioactivities of a Non-Sericin Component from Cocoon Shell Silk Sericin of the Silkworm Bombyx mori","volume":"3","author":"Wang","year":"2012","journal-title":"Food Funct."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"8941","DOI":"10.1073\/pnas.0702860104","article-title":"Carotenoid silk coloration is controlled by a carotenoid-binding protein, a product of the yellow blood gene","volume":"104","author":"Sakudoh","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1271\/bbb.66.1396","article-title":"Purification and identification of flavonoids from the yellow green cocoon shell (Sasammayu) of the silkworm","volume":"66","author":"Kurioka","year":"2002","journal-title":"Bombyx mori. Biosci. Biotechnol. Biochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.fitote.2011.11.014","article-title":"Potent antiviral flavone glycosides from Ficus benjamina leaves","volume":"83","author":"Yarmolinsky","year":"2012","journal-title":"Fitoterapia"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0115475","article-title":"Houttuynia cordata targets the beginning stage of herpes simplex virus infection","volume":"10","author":"Hung","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_48","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_49","doi-asserted-by":"crossref","unstructured":"Kim, C.H., Kim, J.E., and Song, Y.J. (2020). Antiviral activities of quercetin and isoquercitrin against human herpesviruses. Molecules, 25.","DOI":"10.3390\/molecules25102379"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/12\/1553\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:51:55Z","timestamp":1760169115000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/12\/1553"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,19]]},"references-count":49,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["antibiotics10121553"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics10121553","relation":{},"ISSN":["2079-6382"],"issn-type":[{"type":"electronic","value":"2079-6382"}],"subject":[],"published":{"date-parts":[[2021,12,19]]}}}