{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:57:12Z","timestamp":1792807032809,"version":"4.5.0"},"reference-count":76,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Oceans and Fisheries, South Korea","award":["RS-2021-KS211475"],"award-info":[{"award-number":["RS-2021-KS211475"]}],"id":[{"id":"https:\/\/ror.org\/00c5s4a53","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>With emerging viruses and drug resistance on the rise, the discovery and development of innovative antiviral substances and agents are necessary for the effective treatment and control of viral outbreaks. Surrogate viruses are safer alternatives used in research to mimic dangerous or hard-to-culture viruses. They enable efficient, ethical, and cost-effective screening of antiviral compounds. In this study, we used a recombinant viral hemorrhagic septicemia virus (rVHSV) expressing enhanced green fluorescent protein as a surrogate for RNA viruses for the high-throughput screening of antiviral agents. An optimized mixture of viruses and EPC host cells was distributed in 96-well plates containing chemical compounds or plant extracts for screening. Using this system, 44,642 chemical compounds and 8104 plant and marine organism extracts were tested; 140 candidates were selected from primary screening, and 8 compounds and 5 plant extracts were further selected based on the selectivity index (SI), representing the ratio of the cytotoxic concentration (CC50) to the inhibition concentration (IC50). Among these, compound 3, which had the highest SI value of 1046, was further tested, considering in vitro activity against VHSV and another fish rhabdovirus, snakehead rhabdovirus (SHRV).<\/jats:p>","DOI":"10.3390\/v17111522","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T12:02:42Z","timestamp":1763640162000},"page":"1522","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Development of a Mass Antiviral Screening System Using Viral Hemorrhagic Septicemia Virus as an RNA Surrogate and Activity Confirmation with a Fish Rhabdovirus"],"prefix":"10.3390","volume":"17","author":[{"given":"Ji Woo","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Microbiology, School of Marine and Fisheries Sciences, Pukyong National University, Busan 48513, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Marine and Fisheries Sciences, Pukyong National University, Busan 48513, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Jeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Risk Assessment Research Center, Korea Institute of Ocean Science & Technology, Geoje 53201, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6090-507X","authenticated-orcid":false,"given":"Taek-Kyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Risk Assessment Research Center, Korea Institute of Ocean Science & Technology, Geoje 53201, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4923-5121","authenticated-orcid":false,"given":"Tae-Jin","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Marine and Fisheries Sciences, Pukyong National University, Busan 48513, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1128\/JVI.06203-11","article-title":"Reassortment and Mutation of the Avian Influenza Virus Polymerase PA Subunit Overcome Species Barriers","volume":"86","author":"Mehle","year":"2012","journal-title":"J. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Duffy, S. (2018). Why are RNA virus mutation rates so damn high?. PLoS Biol., 16.","DOI":"10.1371\/journal.pbio.3000003"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8399","DOI":"10.1073\/pnas.1208059110","article-title":"Zoonosis emergence linked to agricultural intensification and environmental change","volume":"110","author":"Jones","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.pt.2016.04.007","article-title":"Global Patterns of Zoonotic Disease in Mammals","volume":"32","author":"Han","year":"2016","journal-title":"Trends Parasitol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/j.1600-065X.2008.00737.x","article-title":"Innate immunity to virus infection","volume":"227","author":"Takeuchi","year":"2009","journal-title":"Immunol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3647","DOI":"10.1039\/D0CS01118E","article-title":"Antiviral drug discovery: Preparing for the next pandemic","volume":"50","author":"Adamson","year":"2021","journal-title":"Chem. Soc. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Andrei, G. (2021). Vaccines and Antivirals: Grand Challenges and Great Opportunities. Front. Virol., 1.","DOI":"10.3389\/fviro.2021.666548"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"20587384211002621","DOI":"10.1177\/20587384211002621","article-title":"A review: Mechanism of action of antiviral drugs","volume":"35","author":"Kausar","year":"2021","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1128\/CMR.00102-15","article-title":"Approved Antiviral Drugs over the Past 50 Years","volume":"29","author":"Clercq","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e29369","DOI":"10.1002\/jmv.29369","article-title":"Paving new roads toward the advancement of broad-spectrum antiviral agents","volume":"96","author":"Du","year":"2024","journal-title":"J. Med. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e170236","DOI":"10.1172\/JCI170236","article-title":"Preparing for the next viral threat with broad-spectrum antivirals","volume":"133","author":"Karim","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1021\/acscentsci.0c00984","article-title":"Targeting the SARS-CoV-2 RNA Genome with Small Molecule Binders and Ribonuclease Targeting Chimera (RIBOTAC) Degraders","volume":"6","author":"Haniff","year":"2020","journal-title":"ACS Cent. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e00819","DOI":"10.1128\/AAC.00819-20","article-title":"Identification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs","volume":"64","author":"Jeon","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_14","first-page":"42","article-title":"Technological platforms used for the screening of new antiviral drugs","volume":"4","author":"Ramirez","year":"2018","journal-title":"Int. J. Biosen. Bioelectron."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1002\/jmv.25463","article-title":"An antiviral drug screening system for enterovirus 71 based on an improved plaque assay: A potential high-throughput method","volume":"91","author":"Yin","year":"2019","journal-title":"J. Med. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"104884","DOI":"10.1016\/j.antiviral.2020.104884","article-title":"Generation and characterization of Japanese encephalitis virus expressing GFP reporter gene for high throughput drug screening","volume":"182","author":"Zhang","year":"2020","journal-title":"Antivir. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1007\/s12033-021-00299-7","article-title":"Cell-Based High-Throughput Screening Protocol for Discovering Antiviral Inhibitors Against SARS-COV-2 Main Protease (3CLpro)","volume":"63","author":"Rothan","year":"2021","journal-title":"Mol. Biotechnol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.pathol.2020.09.006","article-title":"Laboratory biosafety measures involving SARS-CoV-2 and the classification as a Risk Group 3 biological agent","volume":"52","author":"Kaufer","year":"2020","journal-title":"Pathology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8692","DOI":"10.1021\/acs.est.7b01296","article-title":"Evaluation of Phi6 Persistence and Suitability as an Enveloped Virus Surrogate","volume":"51","author":"Stachler","year":"2017","journal-title":"Environ. Sci. Technol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Feroz, H., Cetnar, D., Hewlett, R., Sharma, S., Holstein, M., Ghose, S., and Li, Z.J. (2021). Surrogate model to screen for inactivation-based clearance of enveloped viruses during biotherapeutics process development. Biotechnol. J., 16.","DOI":"10.1002\/biot.202100176"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0166-3542(03)00174-8","article-title":"Bovine viral diarrhea virus as a surrogate model of hepatitis C virus for the evaluation of antiviral agents","volume":"60","author":"Buckwold","year":"2003","journal-title":"Antivir. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.antiviral.2013.07.013","article-title":"Cutthroat trout virus as a surrogate in vitro infection model for testing inhibitors of hepatitis E virus replication","volume":"100","author":"Debing","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1111\/j.1749-6632.1965.tb14292.x","article-title":"Research on the virus of Egtved disease","volume":"126","author":"Jensen","year":"1965","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0168-1702(99)00062-3","article-title":"Isolation of viral haemorrhagic septicaemia virus (VHSV) from wild marine fish species in the Baltic Sea, Kattegat, Skagerrak and the North Sea","volume":"63","author":"Mortensen","year":"1999","journal-title":"Virus Res."},{"key":"ref_25","first-page":"186","article-title":"Isolation of viral haemorrhagic septicaemia virus (VHSV) from wild Japanese flounder, Paralichthys olivaceus","volume":"20","author":"Takano","year":"2000","journal-title":"Bull.-Eur. Assoc. Fish Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"211","DOI":"10.3354\/dao055211","article-title":"Host and geographic range extensions of the North American strain of viral hemorrhagic septicemia virus","volume":"55","author":"Hedrick","year":"2003","journal-title":"Dis. Aquat. Org."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/j.1365-2761.2005.00654.x","article-title":"Viral haemorrhagic septicaemia virus in marine fish and its implications for fish farming\u2014A review","volume":"28","author":"Skall","year":"2005","journal-title":"J. Fish Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.virusres.2016.10.010","article-title":"The family Rhabdoviridae: Mono- and bipartite negative-sense RNA viruses with diverse genome organization and common evolutionary origins","volume":"227","author":"Dietzgen","year":"2017","journal-title":"Virus Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Abdellaoui, N., Kim, S.Y., Kim, K.H., and Kim, M.S. (2022). Effects of Non-Virion Gene Expression Level and Viral Genome Length on the Replication and Pathogenicity of Viral Hemorrhagic Septicemia Virus. Viruses, 14.","DOI":"10.3390\/v14091886"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.fsi.2016.09.035","article-title":"Over-passage of epithelioma papulosum cyprini (EPC) cells increased viral hemorrhagic septicemia virus (VHSV) replication","volume":"58","author":"Kim","year":"2016","journal-title":"Fish Shellfish Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"114639","DOI":"10.1016\/j.jviromet.2022.114639","article-title":"Development of rapid neutralization assay of viral hemorrhagic septicemia virus (VHSV) based on chimeric rhabdovirus expressing heterologous glycoprotein","volume":"311","author":"Lee","year":"2023","journal-title":"J. Virol. Methods"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1093\/nar\/26.8.2034","article-title":"Detection of programmed cell death using fluorescence energy transfer","volume":"26","author":"Xu","year":"1998","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Arpino, J.A.J., Rizkallah, P.J., and Jones, D.D. (2012). Crystal Structure of Enhanced Green Fluorescent Protein to 1.35 \u00c5 Resolution Reveals Alternative Conformations for Glu222. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047132"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"108476","DOI":"10.1016\/j.fsi.2022.108476","article-title":"Protection of rainbow trout (Oncorhynchus mykiss) against VHSV genotype Ia and IHNV by immunization with VHSV genotype IVa backbone-based single-cycle viruses","volume":"132","author":"Kim","year":"2023","journal-title":"Fish Shellfish Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3354\/dao02394","article-title":"Generation and characterization of NV gene-knockout recombinant viral hemorrhagic septicemia virus (VHSV) genotype IVa","volume":"97","author":"Kim","year":"2011","journal-title":"Dis. Aquat. Org."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"110280","DOI":"10.1016\/j.fsi.2025.110280","article-title":"In vitro and in vivo infection of snakehead rhabdovirus (SHRV) and recombinant chimeric SHRVs in Penaeus vannamei to evaluate availability as a vector for heterologous protein expression","volume":"161","author":"Choi","year":"2025","journal-title":"Fish Shellfish Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/pst.426","article-title":"Guidelines for accurate EC50\/IC50 estimation","volume":"10","author":"Sebaugh","year":"2011","journal-title":"Pharm. Stat."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1093\/molbev\/msaa247","article-title":"Biased Mutation and Selection in RNA Viruses","volume":"38","author":"Kustin","year":"2020","journal-title":"Mol. Biol. Evol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41564-018-0296-2","article-title":"Tracking virus outbreaks in the twenty-first century","volume":"4","author":"Grubaugh","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"116442","DOI":"10.1016\/j.ejmech.2024.116442","article-title":"Medicinal chemistry strategies toward broad-spectrum antiviral agents to prevent next pandemics","volume":"271","author":"Dai","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_41","first-page":"2","article-title":"High-Throughput Screening: The Hits and Leads of Drug Discovery\u2014An Overview","volume":"1","author":"Martis","year":"2011","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Zang, R., Li, D., Tang, I.-C., Wang, J., and Yang, S.-T. (2012). Cell-based assays in high-throughput screening for drug discovery. Int. J. Biotechnol. Wellness Ind., 1.","DOI":"10.6000\/1927-3037.2012.01.01.02"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.antiviral.2019.05.013","article-title":"Development of a rapid antiviral screening assay based on eGFP reporter virus of Mayaro virus","volume":"168","author":"Li","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Li, W., Zhang, M., Zheng, H., Zhou, P., Liu, Z., Jongkaewwattana, A., Luo, R., and He, Q. (2021). Construction of a Recombinant Porcine Epidemic Diarrhea Virus Encoding Nanoluciferase for High-Throughput Screening of Natural Antiviral Products. Viruses, 13.","DOI":"10.3390\/v13091866"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.virs.2023.06.007","article-title":"A high throughput antiviral screening platform for alphaviruses based on Semliki Forest virus expressing eGFP reporter gene","volume":"38","author":"Shi","year":"2023","journal-title":"Virol. Sin."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"106242","DOI":"10.1016\/j.antiviral.2025.106242","article-title":"High-throughput split-GFP antiviral screening assay against fusogenic paramyxoviruses","volume":"241","author":"Vandemaele","year":"2025","journal-title":"Antivir. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"19111","DOI":"10.1074\/jbc.RA119.010268","article-title":"Facile autofluorescence suppression enabling tracking of single viruses in live cells","volume":"294","author":"Chen","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.dci.2017.07.025","article-title":"Autophagy induced by infectious hematopoietic necrosis virus inhibits intracellular viral replication and extracellular viral yields in epithelioma papulosum cyprini cell line","volume":"77","author":"Zhao","year":"2017","journal-title":"Dev. Comp. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.fsi.2019.08.058","article-title":"Effect of CRISPR\/Cas9-mediated knockout of either Mx1 or ISG15 gene in EPC cells on resistance against VHSV infection","volume":"93","author":"Kim","year":"2019","journal-title":"Fish Shellfish Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"R\u00fcdiger, D., Kupke, S.Y., Laske, T., Zmora, P., and Reichl, U. (2019). Multiscale modeling of influenza A virus replication in cell cultures predicts infection dynamics for highly different infection conditions. PLOS Comput. Biol., 15.","DOI":"10.1371\/journal.pcbi.1006819"},{"key":"ref_51","first-page":"25","article-title":"Evaluation of Multiplicity of Infection (MOI) and Harvesting Time on the Production of CVS-11 Strain of Rabies Virus in BSR Cell Line","volume":"9","author":"Rahpeyma","year":"2021","journal-title":"J. Med. Microbiol. Infect. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0769-2617(83)80060-4","article-title":"Some properties of the Epithelioma papulosum cyprini (EPC) cell line from carp cyprinus carpio","volume":"134","author":"Fijan","year":"1983","journal-title":"Ann. De L\u2019institut Pasteur Virol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Eckhardt, D., Mueller, J., Friedrich, J., Klee, J.-P., Sardlishvili, I., Walter, L.E., Fey, S., Czermak, P., and Salzig, D. (2024). Production of Oncolytic Measles Virus in Vero Cells: Impact of Culture Medium and Multiplicity of Infection. Viruses, 16.","DOI":"10.20944\/preprints202409.1845.v1"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.phymed.2009.08.005","article-title":"Xanthohumol enhances antiviral effect of interferon \u03b1-2b against bovine viral diarrhea virus, a surrogate of hepatitis C virus","volume":"17","author":"Zhang","year":"2010","journal-title":"Phytomedicine"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.4315\/0362-028X.JFP-15-593","article-title":"In Vitro Antiviral Activity of Clove and Ginger Aqueous Extracts against Feline Calicivirus, a Surrogate for Human Norovirus","volume":"79","author":"Aboubakr","year":"2016","journal-title":"J. Food Prot."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1080\/00397911.2021.1925298","article-title":"Synthesis and antiviral evaluation of 5-(arylazo)salicylaldehyde thiosemicarbazone derivatives as potent anti-bovine viral diarrhea virus agents","volume":"51","author":"Basyouni","year":"2021","journal-title":"Synth. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s13567-024-01281-2","article-title":"Construction of recombinant fluorescent LSDV for high-throughput screening of antiviral drugs","volume":"55","author":"Wang","year":"2024","journal-title":"Vet. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"106117","DOI":"10.1016\/j.antiviral.2025.106117","article-title":"Recombinant Pichinde reporter virus as a safe and suitable surrogate for high-throughput antiviral screening against highly pathogenic arenaviruses","volume":"236","author":"Sacramento","year":"2025","journal-title":"Antivir. Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Peng, C., Zhou, Y., Cao, S., Pant, A., Campos Guerrero, M.L., McDonald, P., Roy, A., and Yang, Z. (2020). Identification of Vaccinia Virus Inhibitors and Cellular Functions Necessary for Efficient Viral Replication by Screening Bioactives and FDA-Approved Drugs. Vaccines, 8.","DOI":"10.3390\/vaccines8030401"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Kumar Verma, S., Verma, R., Xue, F., Kumar Thakur, P., Girish, Y.R., and Rakesh, K.P. (2020). Antibacterial activities of sulfonyl or sulfonamide containing heterocyclic derivatives and its structure-activity relationships (SAR) studies: A critical review. Bioorg. Chem., 105.","DOI":"10.1016\/j.bioorg.2020.104400"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Negi, M., Chawla, P.A., Faruk, A., and Chawla, V. (2020). Role of heterocyclic compounds in SARS and SARS CoV-2 pandemic. Bioorg. Chem., 104.","DOI":"10.1016\/j.bioorg.2020.104315"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1002\/jhet.4349","article-title":"Heterocyclic compounds as antiviral drugs: Synthesis, structure\u2013activity relationship and traditional applications","volume":"58","author":"Martins","year":"2021","journal-title":"J. Heterocycl. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1111\/cbdd.13953","article-title":"Synthesis and antiviral activity of diverse heterocyclic scaffolds","volume":"100","author":"Sharma","year":"2022","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"739408","DOI":"10.1016\/j.aquaculture.2023.739408","article-title":"Development of a novel real-time RT-PCR method using peptide nucleic acid (PNA) probes for detecting and genotyping of viral haemorrhagic septicaemia virus (VHSV)","volume":"570","author":"Kim","year":"2023","journal-title":"Aquaculture"},{"key":"ref_65","first-page":"334","article-title":"Rabies is a zoonotic disease: A literature review","volume":"9","author":"Bilal","year":"2021","journal-title":"Occup. Med. Health Aff."},{"key":"ref_66","first-page":"191","article-title":"Viral hemorrhagic septicemia virus (VHSV), past, present and future: A review","volume":"15","author":"Mohammadisefat","year":"2023","journal-title":"Int. Aquat. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.fsi.2015.03.042","article-title":"Identification of regulators of the early stage of viral hemorrhagic septicemia virus infection during curcumin treatment","volume":"45","author":"Jeong","year":"2015","journal-title":"Fish Shellfish Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1007\/s00705-017-3270-z","article-title":"Antiviral effects of extracts from Celosia cristata and Raphanus sativus roots against viral hemorrhagic septicemia virus","volume":"162","author":"Park","year":"2017","journal-title":"Arch. Virol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"108456","DOI":"10.1016\/j.fsi.2022.108456","article-title":"In vitro and in vivo evaluation of the antiviral activity of arctigenin, ribavirin, and ivermectin against viral hemorrhagic septicemia virus infection","volume":"132","author":"Baek","year":"2023","journal-title":"Fish Shellfish Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"740703","DOI":"10.1016\/j.aquaculture.2024.740703","article-title":"Antiviral activity of the coumarin derivative scoparone against viral hemorrhagic septicemia virus in vitro and in the olive flounder Paralichthys olivaceus","volume":"585","author":"Mendis","year":"2024","journal-title":"Aquaculture"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"742770","DOI":"10.1016\/j.aquaculture.2025.742770","article-title":"Antiviral effects of remdesivir on fish viruses from the Rhabdoviridae family","volume":"609","author":"Choi","year":"2025","journal-title":"Aquaculture"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s12275-012-2068-7","article-title":"Antiviral activities of flavonoids isolated from the bark of Rhus verniciflua stokes against fish pathogenic viruses In Vitro","volume":"50","author":"Kang","year":"2012","journal-title":"J. Microbiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.antiviral.2005.02.005","article-title":"The olive leaf extract exhibits antiviral activity against viral haemorrhagic septicaemia rhabdovirus (VHSV)","volume":"66","author":"Micol","year":"2005","journal-title":"Antivir. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"115232","DOI":"10.1016\/j.jviromet.2025.115232","article-title":"Chimeric snakehead rhabdoviruses and zebrafish as a model system for investigating the role of fish rhabdoviral glycoproteins in in vivo virulence","volume":"338","author":"Kim","year":"2025","journal-title":"J. Virol. Methods"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e02021","DOI":"10.1128\/mbio.02021-22","article-title":"Decoding the Role of Temperature in RNA Virus Infections","volume":"13","author":"Bisht","year":"2022","journal-title":"mBio"},{"key":"ref_76","unstructured":"Office International des \u00c9pizooties (2003). Manual of Diagnostic Tests for Aquatic Animals, Paris Office International des \u00c9pizooties. [4th ed.]."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/11\/1522\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T12:07:04Z","timestamp":1763640424000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/11\/1522"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,20]]},"references-count":76,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["v17111522"],"URL":"https:\/\/doi.org\/10.3390\/v17111522","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,20]]}}}