{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:00:02Z","timestamp":1791514802083,"version":"4.3.4"},"reference-count":42,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31860704"],"award-info":[{"award-number":["31860704"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jiangxi Province Project","award":["20192BAB214023"],"award-info":[{"award-number":["20192BAB214023"]}]},{"name":"Jiangxi Province Project","award":["2020ACBL215007"],"award-info":[{"award-number":["2020ACBL215007"]}]},{"name":"Program for Jiangxi Agriculture Research System","award":["JXARS-01"],"award-info":[{"award-number":["JXARS-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Porcine epidemic diarrhea virus (PEDV), an enteric coronavirus, causes neonatal pig acute gastrointestinal infection with a characterization of severe diarrhea, vomiting, high morbidity, and high mortality, resulting in tremendous damages to the swine industry. Neither specific antiviral drugs nor effective vaccines are available, posing a high priority to screen antiviral drugs. The aim of this study is to investigate anti-PEDV effects of carbazole alkaloid derivatives. Eighteen carbazole derivatives (No.1 to No.18) were synthesized, and No.5, No.7, and No.18 were identified to markedly reduce the replication of enhanced green fluorescent protein (EGFP) inserted-PEDV, and the mRNA level of PEDV N. Flow cytometry assay, coupled with CCK8 assay, confirmed No.7 and No.18 carbazole derivatives displayed high inhibition effects with low cell toxicity. Furthermore, time course analysis indicated No.7 and No.18 carbazole derivatives exerted inhibition at the early stage of the viral life cycle. Collectively, the analysis underlines the benefit of carbazole derivatives as potential inhibitors of PEDV, and provides candidates for the development of novel therapeutic agents.<\/jats:p>","DOI":"10.3390\/v13122527","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T21:32:40Z","timestamp":1639690360000},"page":"2527","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Antiviral Activities of Carbazole Derivatives against Porcine Epidemic Diarrhea Virus In Vitro"],"prefix":"10.3390","volume":"13","author":[{"given":"Zheng","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China"},{"name":"Jiangxi Engineering Research Center for Animal Health Products, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6862-677X","authenticated-orcid":false,"given":"Jinfeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China"},{"name":"Jiangxi Engineering Research Center for Animal Health Products, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiying","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiming","family":"Hu","sequence":"additional","affiliation":[{"name":"Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nengshui","family":"Ding","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Pig Genetic Improvement and Production Technology, Jiangxi Agricultural University, Nanchang 330045, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China"},{"name":"Jiangxi Engineering Research Center for Animal Health Products, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deping","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China"},{"name":"Jiangxi Engineering Research Center for Animal Health Products, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6621-6694","authenticated-orcid":false,"given":"Yu","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China"},{"name":"Jiangxi Engineering Research Center for Animal Health Products, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China"},{"name":"Jiangxi Engineering Research Center for Animal Health Products, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5002-5690","authenticated-orcid":false,"given":"Zhen","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China"},{"name":"Jiangxi Engineering Research Center for Animal Health Products, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2715-4005","authenticated-orcid":false,"given":"Shaoyong","family":"Ke","sequence":"additional","affiliation":[{"name":"Hubei Biopesticide Engineering Research Centre, Hubei Academy of Agricultural Sciences, Wuhan 430064, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,16]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/tbed.12991","article-title":"Evolutionary and genotypic analyses of global porcine epidemic diarrhea virus strains","volume":"66","author":"Guo","year":"2019","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.vetmic.2019.07.003","article-title":"Application of RNAscope technology to studying the infection dynamics of a Chinese porcine epidemic diarrhea virus variant strain BJ2011C in neonatal piglets","volume":"235","author":"Cai","year":"2019","journal-title":"Vet. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1111\/tbed.13439","article-title":"A molecular epidemiological investigation of PEDV in China: Characterization of co-infection and genetic diversity of S1-based genes","volume":"67","author":"Su","year":"2020","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.virusres.2016.05.026","article-title":"Porcine epidemic diarrhea in China","volume":"226","author":"Wang","year":"2016","journal-title":"Virus Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/BF01317606","article-title":"A new coronavirus-like particle associated with diarrhea in swine","volume":"58","author":"Pensaert","year":"1978","journal-title":"Arch. Virol."},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"273","DOI":"10.3389\/fvets.2019.00273","article-title":"The Role of Non-animal Origin Feed Ingredients in Transmission of Viral Pathogens of Swine: A Review of Scientific Literature","volume":"6","author":"Gordon","year":"2019","journal-title":"Front. Vet. Sci."},{"key":"ref_9","first-page":"134","article-title":"Porcine epidemic diarrhea virus infection: Etiology, epidemiology, pathogenesis and immunoprophylaxis","volume":"204","author":"Jung","year":"2015","journal-title":"Veter.-J."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Langel, S., Wang, Q., Vlasova, A.N., and Saif, L.J. (2020). Host Factors Affecting Generation of Immunity against Porcine Epidemic Diarrhea Virus in Pregnant and Lactating Swine and Passive Protection of Neonates. Pathogens, 9.","DOI":"10.3390\/pathogens9020130"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1111\/tbed.12823","article-title":"Swine enteric coronavirus disease: A review of 4 years with porcine epidemic diarrhoea virus and porcine deltacoronavirus in the United States and Canada","volume":"65","author":"Niederwerder","year":"2018","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"727","DOI":"10.3389\/fimmu.2019.00727","article-title":"Stage of Gestation at Porcine Epidemic Diarrhea Virus Infection of Pregnant Swine Impacts Maternal Immunity and Lactogenic Immune Protection of Neonatal Suckling Piglets","volume":"10","author":"Langel","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"10825","DOI":"10.1038\/s41598-017-11160-w","article-title":"Virulence of current German PEDV strains in suckling pigs and investigation of protective effects of maternally derived antibodies","volume":"7","author":"Leidenberger","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1089\/vim.2017.0023","article-title":"Effect of Booster Vaccination with Inactivated Porcine Epidemic Diarrhea Virus on Neutralizing Antibody Response in Mammary Secretions","volume":"31","author":"Gillespie","year":"2018","journal-title":"Viral Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.vetmic.2016.11.029","article-title":"Vaccines for porcine epidemic diarrhea virus and other swine coronaviruses","volume":"206","author":"Gerdts","year":"2017","journal-title":"Vet. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1055\/a-1177-4396","article-title":"Challenges at the Time of COVID-19: Opportunities and Innovations in Antivirals from Nature","volume":"86","author":"Hensel","year":"2020","journal-title":"Planta Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4303","DOI":"10.1021\/cr020059j","article-title":"Isolation and synthesis of biologically active carbazole alkaloids","volume":"102","author":"Reddy","year":"2002","journal-title":"Chem. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3193","DOI":"10.1021\/cr200447s","article-title":"Occurrence, biogenesis, and synthesis of biologically active carbazole alkaloids","volume":"112","author":"Schmidt","year":"2012","journal-title":"Chem. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1177\/095632020501600603","article-title":"A novel small molecular weight compound with a carbazole structure that demonstrates potent human immunodeficiency virustype-1 integrase inhibitory activity","volume":"16","author":"Yan","year":"2005","journal-title":"Antivir. Chem. Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Yang, J.-H., Wang, X.-Y., Zhou, Y.-P., Lu, R., Chen, C.-H., Zhang, M.-H., Cheng, Y.-Y., Morris-Natschke, S.L., Lee, K.-H., and Wang, Y.-S. (2019). Carbazole Alkaloids from Clausena anisum-olens: Isolation, Characterization, and Anti-HIV Evaluation. Molecules, 25.","DOI":"10.3390\/molecules25010099"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"O\u2019Rourke, A., Kremb, S., Bader, T.M., Helfer, M., Schmitt-Kopplin, P., Gerwick, W.H., Brack-Werner, R., and Voolstra, C.R. (2016). Alkaloids from the Sponge Stylissa carteri Present Prospective Scaffolds for the Inhibition of Human Immunodeficiency Virus 1 (HIV-1). Mar. Drugs, 14.","DOI":"10.3390\/md14020028"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6063","DOI":"10.1016\/j.bmcl.2009.09.037","article-title":"Design and efficient synthesis of novel arylthioure aderivatives as potent hepatitis C virus inhibitors","volume":"19","author":"Kang","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1021\/acs.jnatprod.5b00325","article-title":"Antiviral Matrine-Type Alkaloids from the Rhizomes of Sophora tonkinensis","volume":"78","author":"Pan","year":"2015","journal-title":"J. Nat. Prod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1248\/cpb.57.1246","article-title":"Isolation of acridone alkaloids and N-[(4-monoterpenyloxy)phenylethyl]-substituted sulfur-containing propanamide derivatives from Glycosmis parva and their anti-herpes simplex virus activity","volume":"57","author":"Chansriniyom","year":"2009","journal-title":"Chem. Pharm. Bull."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s12250-010-3092-6","article-title":"In vitro anti-viral activity of the total alkaloids from Tripterygium hypoglaucum against herpes simplex virus type 1","volume":"25","author":"Ren","year":"2010","journal-title":"Virol. Sin."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Li, C., Li, Z., Zou, Y., Wicht, O., van Kuppeveld, F.J., Rottier, P.J., and Bosch, B.J. (2013). Manipulation of the porcine epidemic diarrhea virus genome using targeted RNA recombination. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0069997"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Li, K., Song, D., Zhang, F., Gong, W., Guo, N., Li, A., Zhou, X., Huang, D., Ye, Y., and Tang, Y. (2018). Complete Genome Sequence of a Recombinant Porcine Epidemic Diarrhea Virus Strain, CH\/JXJA\/2017, Isolated in Jiangxi, China, in 2017. Genome Announc., 6.","DOI":"10.1128\/genomeA.01590-17"},{"key":"ref_28","first-page":"274","article-title":"Application of cell surface-fluorescence immunosorbent assay in rapid screening of a hybridoma secreting monoclonal antibodyagainst PEDV N protein","volume":"42","author":"Luo","year":"2020","journal-title":"Zhongguo Yufang Shouyi Xuebao\/Chin. J. Prev. Vet. Med."},{"key":"ref_29","first-page":"267","article-title":"A systematic review of health economic models and utility estimation methods in schizophrenia","volume":"18","author":"Fasseeh","year":"2018","journal-title":"Expert Rev. Pharm. Outcomes Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ramesh, A.K., Parre\u00f1o, V., Schmidt, P.J., Lei, S., Zhong, W., Jiang, X., Emelko, M.B., and Yuan, L. (2020). Evaluation of the 50% Infectious Dose of Human Norovirus Cin-2 in Gnotobiotic Pigs: A Comparison of Classical and Contemporary Methods for Endpoint Estimation. Viruses, 12.","DOI":"10.3390\/v12090955"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.1016\/S0264-410X(99)00059-6","article-title":"Derivation of attenuated porcine epidemic diarrhea virus (PEDV) as vaccine candidate","volume":"17","author":"Kweon","year":"1999","journal-title":"Vaccine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.virusres.2016.05.016","article-title":"Lactogenic immunity and vaccines for porcine epidemic diarrhea virus (PEDV): Historical and current concepts","volume":"226","author":"Langel","year":"2016","journal-title":"Virus Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Asai, D., and Nakashima, H. (2018). Pathogenic Viruses Commonly Present in the Oral Cavity and Relevant Antiviral Compounds Derived from Natural Products. Medicines, 5.","DOI":"10.3390\/medicines5040120"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1021\/jm501567f","article-title":"Oleanane triterpenes from the flowers of Camellia japonica inhibit porcine epidemic diarrhea virus (PEDV) replication","volume":"58","author":"Yang","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1021\/acs.jnatprod.8b00435","article-title":"Prenylated Phenolic Compounds from the Leaves of Sabia limoniacea and Their Antiviral Activities against Porcine Epidemic Diarrhea Virus","volume":"82","author":"Cho","year":"2019","journal-title":"J. Nat. Prod."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"108849","DOI":"10.1016\/j.vetmic.2020.108849","article-title":"Aloe extract inhibits porcine epidemic diarrhea virus in vitro and in vivo","volume":"249","author":"Xu","year":"2020","journal-title":"Vet. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"197989","DOI":"10.1016\/j.virusres.2020.197989","article-title":"Natural product-derived phytochemicals as potential agents against coronaviruses: A review","volume":"284","author":"Mani","year":"2020","journal-title":"Virus Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Li, Z., Cao, H., Cheng, Y., Zhang, X., Zeng, W., Sun, Y., Chen, S., He, Q., and Han, H. (2020). Inhibition of Porcine Epidemic Diarrhea Virus Replication and Viral 3C-Like Protease by Quercetin. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218095"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1007\/s11262-019-01633-7","article-title":"In vitro antiviral activity of Griffithsin against porcine epidemic diarrhea virus","volume":"55","author":"Li","year":"2019","journal-title":"Virus Genes"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"113009","DOI":"10.1016\/j.jep.2020.113009","article-title":"Antiviral activity against porcine epidemic diarrhea virus of Pogostemon cablin polysaccharide","volume":"259","author":"Chen","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.phymed.2007.07.060","article-title":"Protective roles of puerarin and Danshensu on acute ischemic myocardial injury in rats","volume":"14","author":"Wu","year":"2007","journal-title":"Phytomedicine"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3389\/fimmu.2020.00169","article-title":"Quantitative Proteomic Analysis Reveals Antiviral and Anti-inflammatory Effects of Puerarin in Piglets Infected With Porcine Epidemic Diarrhea Virus","volume":"11","author":"Wu","year":"2020","journal-title":"Front. Immunol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/12\/2527\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:49:23Z","timestamp":1760168963000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/12\/2527"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,16]]},"references-count":42,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["v13122527"],"URL":"https:\/\/doi.org\/10.3390\/v13122527","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,16]]}}}