{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T10:00:47Z","timestamp":1784800847009,"version":"3.55.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25fk0310525"],"award-info":[{"award-number":["JP25fk0310525"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"MEXT","doi-asserted-by":"publisher","award":["JP25K21782"],"award-info":[{"award-number":["JP25K21782"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"MEXT","doi-asserted-by":"publisher","award":["JP24K02290"],"award-info":[{"award-number":["JP24K02290"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"MEXT","doi-asserted-by":"publisher","award":["JP24K18457"],"award-info":[{"award-number":["JP24K18457"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001695","name":"JST","doi-asserted-by":"publisher","award":["JPMJMI22G1"],"award-info":[{"award-number":["JPMJMI22G1"]}],"id":[{"id":"10.13039\/501100001695","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, regulates the metabolism of exogenous compounds. Pharmacological inhibition of AhR reduces lipid droplet (LD) accumulation and suppresses hepatitis C virus (HCV) proliferation. Recent evidence implicates AhR in the propagation of viruses such as herpes simplex virus type 1 (HSV-1), making it a host factor regulating the proliferation of diverse viruses and an attractive target for broad-spectrum antivirals. To identify AhR ligands with antiviral activity, we screened secondary metabolites derived from fungi isolated from various animals. We identified roquefortine C, an indole alkaloid obtained from quail-derived fungi, as an AhR antagonist. Roquefortine C suppressed LD formation and HCV production in human hepatoma cells. Additionally, it showed anti-HSV-1 and anti-pseudorabies virus (PRV) activities. Notably, our study demonstrated the relationship between AhR and PRV for the first time. AhR ligands could represent potential lead compounds with broad-spectrum antiviral properties.<\/jats:p>","DOI":"10.1093\/bbb\/zbag070","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T14:14:16Z","timestamp":1778854456000},"page":"986-991","source":"Crossref","is-referenced-by-count":0,"title":["Roquefortine C isolated from a quail feces-derived fungus exhibits aryl hydrocarbon receptor antagonistic and broad-spectrum antiviral activities"],"prefix":"10.1093","volume":"90","author":[{"given":"Karin","family":"Maruyama","sequence":"first","affiliation":[{"name":"School of Veterinary Medicine, Azabu University , Chuo-ku, Sagamihara ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kou","family":"Nakamura","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, Azabu University , Chuo-ku, Sagamihara ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuki","family":"Yasukochi","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, Azabu University , Chuo-ku, Sagamihara ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Ohashi","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases, Japan Institute for Health Security Department of Drug Development, , Shinjuku-ku, Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shogo","family":"Nakajima","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, Azabu University , Chuo-ku, Sagamihara ,","place":["Japan"]},{"name":"National Institute of Infectious Diseases, Japan Institute for Health Security Department of Drug Development, , Shinjuku-ku, Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiki","family":"Saitoh","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, Azabu University , Chuo-ku, Sagamihara ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nozomi","family":"Mosu","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, Azabu University , Chuo-ku, Sagamihara ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namiho","family":"Suzuki","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, Azabu University , Chuo-ku, Sagamihara ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chihiro","family":"Kase","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, Azabu University , Chuo-ku, Sagamihara ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoyuki","family":"Aihara","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, Azabu University , Chuo-ku, Sagamihara ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7560-4445","authenticated-orcid":false,"given":"Hironobu","family":"Murakami","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, Azabu University , Chuo-ku, Sagamihara ,","place":["Japan"]},{"name":"Center for Human and Animal Symbiosis Science, Azabu University , Chuo-ku, Sagamihara ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiko","family":"Okada","sequence":"additional","affiliation":[{"name":"School of Bioscience and Biotechnology, Tokyo University of Technology , Hachioji, Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan","family":"Fujino","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, Azabu University , Chuo-ku, Sagamihara ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Watashi","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases, Japan Institute for Health Security Department of Drug Development, , Shinjuku-ku, Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8773-3909","authenticated-orcid":false,"given":"Shinji","family":"Kamisuki","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, Azabu University , Chuo-ku, Sagamihara ,","place":["Japan"]},{"name":"Center for Human and Animal Symbiosis Science, Azabu University , Chuo-ku, Sagamihara ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"2026072305011562200_bib1","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1021\/tx015512l","article-title":"Molecular requirements for inhibition of cytochrome p450 activities by roquefortine","volume":"14","author":"Aninat","year":"2001","journal-title":"Chem Res Toxicol"},{"key":"2026072305011562200_bib2","doi-asserted-by":"publisher","first-page":"1421346","DOI":"10.3389\/fimmu.2024.1421346","article-title":"Aryl hydrocarbon receptor: current perspectives on key signaling partners and immunoregulatory role in inflammatory diseases","volume":"15","author":"Bahman","year":"2024","journal-title":"Front Immunol"},{"key":"2026072305011562200_bib3","doi-asserted-by":"publisher","first-page":"101492","DOI":"10.1016\/j.coviro.2025.101492","article-title":"Host-targeted antivirals as broad-spectrum inhibitors of respiratory viruses","volume":"73","author":"Beran","year":"2025","journal-title":"Curr Opin Virol"},{"key":"2026072305011562200_bib4","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1007\/s00281-021-00867-8","article-title":"The aryl hydrocarbon receptor in liver inflammation","volume":"43","author":"Carambia","year":"2021","journal-title":"Semin Immunopathol"},{"key":"2026072305011562200_bib5","doi-asserted-by":"publisher","first-page":"e0047321","DOI":"10.1128\/Spectrum.00473-21","article-title":"Targeting aryl hydrocarbon receptor signaling enhances type I interferon-independent resistance to herpes simplex virus","volume":"9","author":"Chen","year":"2021","journal-title":"Microbiol Spectr"},{"key":"2026072305011562200_bib6","doi-asserted-by":"publisher","first-page":"628821","DOI":"10.3389\/fonc.2021.628821","article-title":"Cancer associated fibroblasts promote renal cancer progression through a TDO\/Kyn\/AhR dependent signaling pathway","volume":"11","author":"Chen","year":"2021","journal-title":"Front Oncol"},{"key":"2026072305011562200_bib7","doi-asserted-by":"publisher","first-page":"8303","DOI":"10.1007\/s00253-016-7788-x","article-title":"Biosynthetic gene clusters for relevant secondary metabolites produced by Penicillium roqueforti in blue cheeses","volume":"100","author":"Garc\u00eda-Estrada","year":"2016","journal-title":"Appl Microbiol Biotechnol"},{"key":"2026072305011562200_bib8","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1038\/s41593-020-0664-0","article-title":"AHR is a Zika virus host factor and a candidate target for antiviral therapy","volume":"23","author":"Giovannoni","year":"2021","journal-title":"Nat Neurosci"},{"key":"2026072305011562200_bib9","doi-asserted-by":"publisher","first-page":"5148","DOI":"10.1038\/s41467-021-25412-x","article-title":"AHR signaling is induced by infection with coronaviruses","volume":"12","author":"Giovannoni","year":"2021","journal-title":"Nat Commun"},{"key":"2026072305011562200_bib10","doi-asserted-by":"publisher","first-page":"464","DOI":"10.3390\/v16030464","article-title":"Brincidofovir effectively inhibits proliferation of pseudorabies virus by disrupting viral replication","volume":"16","author":"Guo","year":"2024","journal-title":"Viruses"},{"key":"2026072305011562200_bib11","doi-asserted-by":"publisher","first-page":"1548038","DOI":"10.3389\/fcimb.2025.1548038","article-title":"Aryl hydrocarbon receptor facilitates HSV-1 lytic infection by enhancing viral gene transcription and receptor expression","volume":"15","author":"Huang","year":"2025","journal-title":"Front Cell Infect Microbiol"},{"key":"2026072305011562200_bib12","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1038\/s41429-019-0213-9","article-title":"Novel neuroprotective hydroquinones with a vinyl alkyne from the fungus, Pestalotiopsis microspora","volume":"72","author":"Kanno","year":"2019","journal-title":"J Antibiot"},{"key":"2026072305011562200_bib13","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/s10295-015-1723-5","article-title":"Natural product discovery: past, present, and future","volume":"43","author":"Katz","year":"2016","journal-title":"J Ind Microbiol Biotechnol"},{"key":"2026072305011562200_bib14","doi-asserted-by":"publisher","first-page":"1871","DOI":"10.1124\/mol.105.021832","article-title":"Novel compound 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazo-phenyl)-amide (CH-223191) prevents 2,3,7,8-TCDD-induced toxicity by antagonizing the aryl hydrocarbon receptor","volume":"69","author":"Kim","year":"2006","journal-title":"Mol Pharmacol"},{"key":"2026072305011562200_bib15","doi-asserted-by":"publisher","first-page":"2522","DOI":"10.1111\/brv.12765","article-title":"Diverse roles of microbial indole compounds in eukaryotic systems","volume":"96","author":"Kumar","year":"2021","journal-title":"Biol Rev Camb Philos Soc"},{"key":"2026072305011562200_bib16","doi-asserted-by":"publisher","first-page":"954","DOI":"10.3390\/jof9100954","article-title":"PrlaeA affects the production of roquefortine C, mycophenolic acid, and andrastin A in Penicillium roqueforti, but it has little impact on asexual development","volume":"9","author":"Marcano","year":"2023","journal-title":"J Fungi"},{"key":"2026072305011562200_bib17","doi-asserted-by":"publisher","first-page":"4325","DOI":"10.1016\/j.bmcl.2015.07.067","article-title":"Isolation and structure of vanitaracin A, a novel anti-hepatitis B virus compound from Talaromyces sp","volume":"25","author":"Matsunaga","year":"2015","journal-title":"Bioorg Med Chem Lett"},{"key":"2026072305011562200_bib18","doi-asserted-by":"publisher","first-page":"e22232","DOI":"10.1002\/ddr.22232","article-title":"Identification of aryl hydrocarbon receptor allosteric antagonists from clinically approved drugs","volume":"85","author":"Mosa","year":"2024","journal-title":"Drug Dev Res"},{"key":"2026072305011562200_bib19","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/s41429-024-00740-4","article-title":"Isolation, structural determination, and antiviral activities of a novel alanine-conjugated polyketide from Talaromyces sp","volume":"77","author":"Mosu","year":"2024","journal-title":"J Antibiot"},{"key":"2026072305011562200_bib20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.virol.2021.06.010","article-title":"Specific antiviral effect of violaceoid E on bovine leukemia virus","volume":"562","author":"Murakami","year":"2021","journal-title":"Virology"},{"key":"2026072305011562200_bib21","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/j.bbrc.2013.09.100","article-title":"Specific inhibition of hepatitis C virus entry into host hepatocytes by fungi-derived sulochrin and its derivatives","volume":"440","author":"Nakajima","year":"2013","journal-title":"Biochem Biophys Res Commun"},{"key":"2026072305011562200_bib22","doi-asserted-by":"publisher","first-page":"9058","DOI":"10.1128\/JVI.00856-16","article-title":"Fungus-derived neoechinulin B as a novel antagonist of liver X receptor, identified by chemical genetics using a hepatitis C virus cell culture system","volume":"90","author":"Nakajima","year":"2016","journal-title":"J Virol"},{"key":"2026072305011562200_bib23","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1248\/cpb.c23-00243","article-title":"Identification of methylsulochrin as a partial agonist for aryl hydrocarbon receptors and its antiviral and anti-inflammatory activities","volume":"71","author":"Nakamura","year":"2023","journal-title":"Chem Pharm Bull"},{"key":"2026072305011562200_bib24","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural products as sources of new drugs over the nearly four decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J Nat Prod"},{"key":"2026072305011562200_bib25","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1021\/acs.jnatprod.5b00555","article-title":"Anti-hepatitis C virus natural product from a fungus, Penicillium herquei","volume":"79","author":"Nishikori","year":"2016","journal-title":"J Nat Prod"},{"key":"2026072305011562200_bib26","doi-asserted-by":"publisher","first-page":"19559","DOI":"10.1074\/jbc.RA118.005033","article-title":"The aryl hydrocarbon receptor\u2013cytochrome P450 1A1 pathway controls lipid accumulation and enhances the permissiveness for hepatitis C virus assembly","volume":"293","author":"Ohashi","year":"2018","journal-title":"J Biol Chem"},{"key":"2026072305011562200_bib27","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1128\/MMBR.69.3.462-500.2005","article-title":"Molecular biology of pseudorabies virus: impact on neurovirology and veterinary medicine","volume":"69","author":"Pomeranz","year":"2005","journal-title":"Microbiol Mol Biol Rev"},{"key":"2026072305011562200_bib28","doi-asserted-by":"publisher","first-page":"6281","DOI":"10.1021\/ja800067q","article-title":"The total synthesis of roquefortine C and a rationale for the thermodynamic stability of isoroquefortine C over roquefortine C","volume":"130","author":"Shangguan","year":"2008","journal-title":"J Am Chem Soc"},{"key":"2026072305011562200_bib29","doi-asserted-by":"publisher","first-page":"eadf0211","DOI":"10.1126\/sciadv.adf0211","article-title":"Aryl hydrocarbon receptor is a proviral host factor and a candidate pan-SARS-CoV-2 therapeutic target","volume":"9","author":"Shi","year":"2023","journal-title":"Sci Adv"},{"key":"2026072305011562200_bib30","doi-asserted-by":"publisher","first-page":"115371","DOI":"10.1016\/j.bcp.2022.115371","article-title":"Functions of the aryl hydrocarbon receptor (AHR) beyond the canonical AHR\/ARNT signaling pathway","volume":"208","author":"Sondermann","year":"2023","journal-title":"Biochem Pharmacol"},{"key":"2026072305011562200_bib31","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/s41573-023-00692-8","article-title":"Accelerating antiviral drug discovery: lessons from COVID-19","volume":"22","author":"Von\u00a0Delft","year":"2023","journal-title":"Nat Rev Drug Discov"},{"key":"2026072305011562200_bib32","doi-asserted-by":"publisher","first-page":"3389","DOI":"10.1021\/acsomega.4c06508","article-title":"Design of the inhibitors for pseudorabies virus replication by reinforcement learning from HSV-1 DNA polymerase inhibitors","volume":"10","author":"Wei","year":"2025","journal-title":"ACS Omega"},{"key":"2026072305011562200_bib33","doi-asserted-by":"publisher","first-page":"116761","DOI":"10.1016\/j.bcp.2025.116761","article-title":"The AHR\u2013NRF2\u2013JDP2 gene battery: ligand\u2013induced AHR transcriptional activation","volume":"233","author":"Wuputra","year":"2025","journal-title":"Biochem Pharmacol"},{"key":"2026072305011562200_bib34","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s13567-023-01171-z","article-title":"Membrane fusion, potential threats, and natural antiviral drugs of pseudorabies virus","volume":"54","author":"Ye","year":"2023","journal-title":"Vet Res"},{"key":"2026072305011562200_bib35","doi-asserted-by":"publisher","first-page":"928","DOI":"10.3390\/v14050928","article-title":"A broad antiviral strategy: inhibitors of human DHODH pave the way for host-targeting antivirals against emerging and re-emerging viruses","volume":"14","author":"Zheng","year":"2022","journal-title":"Viruses"},{"key":"2026072305011562200_bib36","doi-asserted-by":"publisher","first-page":"517","DOI":"10.3389\/fmicb.2015.00517","article-title":"Broad-spectrum antiviral agents","volume":"6","author":"Zhu","year":"2015","journal-title":"Front Microbiol"}],"container-title":["Bioscience, Biotechnology, and Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bbb\/advance-article-pdf\/doi\/10.1093\/bbb\/zbag070\/68292521\/zbag070.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bbb\/article-pdf\/90\/8\/986\/68292521\/zbag070.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bbb\/article-pdf\/90\/8\/986\/68292521\/zbag070.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T09:01:38Z","timestamp":1784797298000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bbb\/article\/90\/8\/986\/8678859"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,15]]},"references-count":36,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,5,15]]},"published-print":{"date-parts":[[2026,7,23]]}},"URL":"https:\/\/doi.org\/10.1093\/bbb\/zbag070","relation":{},"ISSN":["1347-6947"],"issn-type":[{"value":"1347-6947","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,8]]},"published":{"date-parts":[[2026,5,15]]}}}