{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T19:15:28Z","timestamp":1773688528030,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,9,29]],"date-time":"2018-09-29T00:00:00Z","timestamp":1538179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["507294-16"],"award-info":[{"award-number":["507294-16"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Herpes simplex virus (HSV) infections can be treated with direct acting antivirals like acyclovir and foscarnet, but long-term use can lead to drug resistance, which motivates research into broadly-acting antivirals that can provide a greater genetic barrier to resistance. Photodynamic inactivation (PDI) employs a photosensitizer, light, and oxygen to create a local burst of reactive oxygen species that inactivate microorganisms. The botanical plant extract OrthoquinTM is a powerful photosensitizer with antimicrobial properties. Here we report that Orthoquin also has antiviral properties. Photoactivated Orthoquin inhibited herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) infection of target cells in a dose-dependent manner across a broad range of sub-cytotoxic concentrations. HSV inactivation required direct contact between Orthoquin and the inoculum, whereas pre-treatment of target cells had no effect. Orthoquin did not cause appreciable damage to viral capsids or premature release of viral genomes, as measured by qPCR for the HSV-1 genome. By contrast, immunoblotting for HSV-1 antigens in purified virion preparations suggested that higher doses of Orthoquin had a physical impact on certain HSV-1 proteins that altered protein mobility or antigen detection. Orthoquin PDI also inhibited the non-enveloped adenovirus (AdV) in a dose-dependent manner, whereas Orthoquin-mediated inhibition of the enveloped vesicular stomatitis virus (VSV) was light-independent. Together, these findings suggest that the broad antiviral effects of Orthoquin-mediated PDI may stem from damage to viral attachment proteins.<\/jats:p>","DOI":"10.3390\/v10100532","type":"journal-article","created":{"date-parts":[[2018,10,2]],"date-time":"2018-10-02T08:23:50Z","timestamp":1538468630000},"page":"532","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Photodynamic Inactivation of Herpes Simplex Viruses"],"prefix":"10.3390","volume":"10","author":[{"given":"Andrea L.-A.","family":"Monjo","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Dalhousie University, 5850 College Street, Halifax, NS B3H 4R2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3667-4595","authenticated-orcid":false,"given":"Eric S.","family":"Pringle","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dalhousie University, 5850 College Street, Halifax, NS B3H 4R2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mackenzie","family":"Thornbury","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dalhousie University, 5850 College Street, Halifax, NS B3H 4R2, Canada"},{"name":"Department of Pathology and Cell Biology, University of Montreal, V-541 Pavillon Roger Gaudry, 2900 Boulevard \u00c9douard-Montpetit, Montreal, QC H3C 3J7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brett A.","family":"Duguay","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dalhousie University, 5850 College Street, Halifax, NS B3H 4R2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan M. A.","family":"Monro","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Acadia University, 6 University Avenue, Wolfville, NS B4P 2R6, Canada"},{"name":"Photodynamic, Inc., 1344 Summer Street, Halifax, NS B3H 0A8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Hetu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Acadia University, 6 University Avenue, Wolfville, NS B4P 2R6, Canada"},{"name":"Photodynamic, Inc., 1344 Summer Street, Halifax, NS B3H 0A8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danika","family":"Knight","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dalhousie University, 5850 College Street, Halifax, NS B3H 4R2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin G.","family":"Cameron","sequence":"additional","affiliation":[{"name":"Photodynamic, Inc., 1344 Summer Street, Halifax, NS B3H 0A8, Canada"},{"name":"Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, 301 McIver Street, Greensboro, NC 27402, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8028-5055","authenticated-orcid":false,"given":"Sherri A.","family":"McFarland","sequence":"additional","affiliation":[{"name":"Photodynamic, Inc., 1344 Summer Street, Halifax, NS B3H 0A8, Canada"},{"name":"Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, 301 McIver Street, Greensboro, NC 27402, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2794-3722","authenticated-orcid":false,"given":"Craig","family":"McCormick","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dalhousie University, 5850 College Street, Halifax, NS B3H 4R2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,9,29]]},"reference":[{"key":"ref_1","unstructured":"Fields, B.N., Knipe, D.M., and Howley, P.M. (2013). Fields Virology, Wolters Kluwer Health\/Lippincott Williams & Wilkins."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1111\/j.1462-5822.2004.00389.x","article-title":"Herpes simplex virus: Receptors and ligands for cell entry","volume":"6","author":"Spear","year":"2004","journal-title":"Cell. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.cppeds.2008.10.003","article-title":"Persistent and recurring viral infections: The human herpesviruses","volume":"39","author":"Schleiss","year":"2009","journal-title":"Curr. Probl. Pediatr. Adolesc. Health Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3S","DOI":"10.1016\/0002-9343(92)90329-A","article-title":"Mechanism of action of foscarnet against viral polymerases","volume":"92","author":"Crumpacker","year":"1992","journal-title":"Am. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1128\/CMR.16.1.114-128.2003","article-title":"Herpes simplex virus resistance to acyclovir and penciclovir after two decades of antiviral therapy","volume":"16","author":"Bacon","year":"2003","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_6","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_7","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1002\/rmv.1787","article-title":"Antiviral drug resistance in herpesviruses other than cytomegalovirus","volume":"24","author":"Piret","year":"2014","journal-title":"Rev. Med. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1111\/j.1749-6632.1994.tb38949.x","article-title":"n-Docosanol: Broad Spectrum Anti-Viral Activity against Lipid-enveloped Virusesa","volume":"724","author":"Katz","year":"1994","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0166-3542(98)00048-5","article-title":"The anti-herpes simplex virus activity of n-docosanol includes inhibition of the viral entry process","volume":"40","author":"Pope","year":"1998","journal-title":"Antivir. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/978-1-60761-697-9_12","article-title":"Antimicrobial photodynamic inactivation and photodynamic therapy for infections","volume":"635","author":"Huang","year":"2010","journal-title":"Methods Mol. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/j.1751-1097.1992.tb04222.x","article-title":"How does photodynamic therapy work?","volume":"55","author":"Henderson","year":"1992","journal-title":"Photochem. Photobiol."},{"key":"ref_12","unstructured":"Bonnett, R. (2014). Chemical Aspects of Photodynamic Therapy, CRC Press."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Van Straten, D., Mashayekhi, V., de Bruijn, H.S., Oliveira, S., and Robinson, D.J. (2017). Oncologic Photodynamic Therapy: Basic Principles, Current Clinical Status and Future Directions. Cancers, 9.","DOI":"10.3390\/cancers9020019"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wormald, R., Evans, J., Smeeth, L., and Henshaw, K. (2005). Photodynamic therapy for neovascular age-related macular degeneration. Cochrane Database Syst. Rev.","DOI":"10.1002\/14651858.CD002030.pub2"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.3390\/v4071034","article-title":"Photodynamic inactivation of mammalian viruses and bacteriophages","volume":"4","author":"Costa","year":"2012","journal-title":"Viruses"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S1572-1000(05)00007-4","article-title":"Mechanisms in photodynamic therapy: Part one\u2014Photosensitizers, photochemistry and cellular localization","volume":"1","author":"Castano","year":"2004","journal-title":"Photodiagn. Photodyn. Ther."},{"key":"ref_17","unstructured":"McFarland, S. (2017). Novel Polygonum Cuspidatum Extracts and Their Use as Photodynamic Inactivating Agents. (US20170095521A1), U.S. Patent."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/1743-422X-3-63","article-title":"New low-viscosity overlay medium for viral plaque assays","volume":"3","author":"Matrosovich","year":"2006","journal-title":"Virol. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8605","DOI":"10.1128\/JVI.00904-08","article-title":"Comprehensive characterization of extracellular herpes simplex virus type 1 virions","volume":"82","author":"Loret","year":"2008","journal-title":"J. Virol."},{"key":"ref_21","unstructured":"State Pharmacopoeia Commission of the PRC (2008). Pharmacopoeia of the People\u2019s Republic of China 2005, BC Decker, Inc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S1011-1344(98)00124-9","article-title":"Herpes simplex virus proteins are damaged following photodynamic inactivation with phthalocyanines","volume":"44","author":"Smetana","year":"1998","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/1011-1344(93)06949-4","article-title":"Photodynamic inactivation of herpes viruses with phthalocyanine derivatives","volume":"22","author":"Smetana","year":"1994","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/1011-1344(95)07150-Z","article-title":"Inactivation of viruses by chemically and photochemically generated singlet molecular oxygen","volume":"30","author":"Mohr","year":"1995","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1042\/BST0380050","article-title":"Antiviral activity of resveratrol","volume":"38","author":"Campagna","year":"2010","journal-title":"Biochem. Soc. Trans."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"184241","DOI":"10.1155\/2015\/184241","article-title":"Antiviral Activity of Resveratrol against Human and Animal Viruses","volume":"2015","author":"Abba","year":"2015","journal-title":"Adv. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/BF01923366","article-title":"Antiviral activities of anthraquinones, bianthrones and hypericin derivatives from lichens","volume":"52","author":"Cohen","year":"1996","journal-title":"Experientia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/0166-3542(92)90091-I","article-title":"Evaluation of the antiviral activity of anthraquinones, anthrones and anthraquinone derivatives against human cytomegalovirus","volume":"17","author":"Barnard","year":"1992","journal-title":"Antivir. Res."},{"key":"ref_29","first-page":"BR302","article-title":"Inhibition of the replication of hepatitis B virus in vitro by emodin","volume":"12","author":"Dang","year":"2006","journal-title":"Med. Sci. Monit."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lin, C.J., Lin, H.J., Chen, T.H., Hsu, Y.-A., Liu, C.-S., Hwang, G.-Y., and Wan, L. (2015). Polygonum cuspidatum and its active components inhibit replication of the influenza virus through toll-like receptor 9-induced interferon beta expression. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0117602"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/0166-3542(90)90071-E","article-title":"Anthraquinones as a new class of antiviral agents against human immunodeficiency virus","volume":"13","author":"Schinazi","year":"1990","journal-title":"Antivir. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1021\/np50065a012","article-title":"Studies on inhibitors of skin tumor promotion, VI. Inhibitory effects of quinones on Epstein-Barr virus activation","volume":"52","author":"Konoshima","year":"1989","journal-title":"J. Nat. Prod."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0166-3542(01)00125-5","article-title":"In vitro antiviral activity of the anthraquinone chrysophanic acid against poliovirus","volume":"49","author":"Semple","year":"2001","journal-title":"Antivir. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.antiviral.2006.04.014","article-title":"Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction","volume":"74","author":"Ho","year":"2007","journal-title":"Antivir. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/bjp.2008.242","article-title":"Emodin is a novel alkaline nuclease inhibitor that suppresses herpes simplex virus type 1 yields in cell cultures","volume":"155","author":"Hsiang","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1055\/s-1999-13953","article-title":"Emodin, an anthraquinone derivative isolated from the rhizomes of Rheum palmatum, selectively inhibits the activity of casein kinase II as a competitive inhibitor","volume":"65","author":"Yim","year":"1999","journal-title":"Planta Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"14566","DOI":"10.1074\/jbc.M116.714766","article-title":"Cellular Casein Kinase 2 and Protein Phosphatase 2A Modulate Replication Site Assembly of Bluetongue Virus","volume":"291","author":"Mohl","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.virol.2011.12.003","article-title":"Casein kinase 2 regulates vaccinia virus actin tail formation","volume":"423","author":"Alvarez","year":"2012","journal-title":"Virology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.antiviral.2011.06.009","article-title":"CK2 inhibitors increase the sensitivity of HSV-1 to interferon-\u03b2","volume":"91","author":"Smith","year":"2011","journal-title":"Antivir. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1128\/JVI.02339-08","article-title":"Interaction of human cytomegalovirus pUL84 with casein kinase 2 is required for oriLyt-dependent DNA replication","volume":"83","author":"Gao","year":"2009","journal-title":"J. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.bcp.2004.04.012","article-title":"Membrane-related effects underlying the biological activity of the anthraquinones emodin and barbaloin","volume":"68","author":"Alves","year":"2004","journal-title":"Biochem. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11401","DOI":"10.1021\/bi991147+","article-title":"Targeted cross-linking of a molten globule form of acetylcholinesterase by the virucidal agent hypericin","volume":"38","author":"Weiner","year":"1999","journal-title":"Biochemistry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1128\/AAC.35.12.2463","article-title":"Inactivation of enveloped viruses by anthraquinones extracted from plants","volume":"35","author":"Sydiskis","year":"1991","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.ijantimicag.2008.04.018","article-title":"Aloe-emodin is an interferon-inducing agent with antiviral activity against Japanese encephalitis virus and enterovirus 71","volume":"32","author":"Lin","year":"2008","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1128\/JCM.42.1.242-249.2004","article-title":"Surveillance network for herpes simplex virus resistance to antiviral drugs: 3-Year follow-up","volume":"42","author":"Aymard","year":"2004","journal-title":"J. Clin. Microbiol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/10\/10\/532\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:23:09Z","timestamp":1760196189000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/10\/10\/532"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,29]]},"references-count":45,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2018,10]]}},"alternative-id":["v10100532"],"URL":"https:\/\/doi.org\/10.3390\/v10100532","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints201809.0125.v1","asserted-by":"object"}]},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,29]]}}}