{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T06:54:03Z","timestamp":1792738443346,"version":"4.5.0"},"reference-count":56,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2006,4,1]],"date-time":"2006-04-01T00:00:00Z","timestamp":1143849600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2006,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Triaryl pyrazoline {[5-(4-chloro-phenyl)-3-thiophen-2-yl-4,5-dihydro-pyrazol-1-yl]-phenyl-methanone} inhibits flavivirus infection in cell culture. The inhibitor was identified through high-throughput screening of a compound library using a luciferase-expressing West Nile (WN) virus infection assay. The compound inhibited an epidemic strain of WN virus without detectable cytotoxicity (a 50% effective concentration of 28 \u03bcM and a compound concentration of \u2265300 \u03bcM required to reduce 50% cell viability). Besides WN virus, the compound also inhibited other flaviviruses (dengue, yellow fever, and St. Louis encephalitis viruses), an alphavirus (Western equine encephalitis virus), a coronavirus (mouse hepatitis virus), and a rhabdovirus (vesicular stomatitis virus). However, the compound did not suppress an orthomyxovirus (influenza virus) or a retrovirus (human immunodeficiency virus type 1). Mode-of-action analyses in WN virus showed that the compound did not inhibit viral entry or virion assembly but specifically suppressed viral RNA synthesis. To examine the mechanism of inhibition of dengue virus, we developed two replicon systems for dengue type 1 virus: (i) a stable cell line that harbored replicons containing a luciferase reporter and a neomycin phosphotransferase selection marker and (ii) a luciferase-expressing replicon that could differentiate between viral translation and RNA replication. Analyses of the compound in the dengue type 1 virus replicon systems showed that it weakly suppressed viral translation but significantly inhibited viral RNA synthesis. Overall, the results demonstrate that triaryl pyrazoline exerts a broad spectrum of antiflavivirus activity through potent inhibition of viral RNA replication. This novel inhibitor could be developed for potential treatment of flavivirus infection.<\/jats:p>","DOI":"10.1128\/aac.50.4.1320-1329.2006","type":"journal-article","created":{"date-parts":[[2006,3,28]],"date-time":"2006-03-28T22:03:12Z","timestamp":1143583392000},"page":"1320-1329","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":99,"title":["Triaryl Pyrazoline Compound Inhibits Flavivirus RNA Replication"],"prefix":"10.1128","volume":"50","author":[{"given":"Francesc","family":"Puig-Basagoiti","sequence":"first","affiliation":[{"name":"Wadsworth Center, New York State Department of Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Tilgner","sequence":"additional","affiliation":[{"name":"Wadsworth Center, New York State Department of Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett M.","family":"Forshey","sequence":"additional","affiliation":[{"name":"Wadsworth Center, New York State Department of Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean M.","family":"Philpott","sequence":"additional","affiliation":[{"name":"Wadsworth Center, New York State Department of Health"},{"name":"Department of Biomedical Sciences, University at Albany, State University of New York, Albany, New York 12208"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel G.","family":"Espina","sequence":"additional","affiliation":[{"name":"Wadsworth Center, New York State Department of Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Wentworth","sequence":"additional","affiliation":[{"name":"Wadsworth Center, New York State Department of Health"},{"name":"Department of Biomedical Sciences, University at Albany, State University of New York, Albany, New York 12208"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott J.","family":"Goebel","sequence":"additional","affiliation":[{"name":"Wadsworth Center, New York State Department of Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S.","family":"Masters","sequence":"additional","affiliation":[{"name":"Wadsworth Center, New York State Department of Health"},{"name":"Department of Biomedical Sciences, University at Albany, State University of New York, Albany, New York 12208"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Falgout","sequence":"additional","affiliation":[{"name":"U.S. Food and Drug Administration, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Ren","sequence":"additional","affiliation":[{"name":"Wadsworth Center, New York State Department of Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Center for Drug Design, University of Minnesota, Minneapolis, Minnesota 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Yong","family":"Shi","sequence":"additional","affiliation":[{"name":"Wadsworth Center, New York State Department of Health"},{"name":"Department of Biomedical Sciences, University at Albany, State University of New York, Albany, New York 12208"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.24.12925-12933.2002"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2005.06.009"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.5.1231-1239.2002"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-67-2-229"},{"key":"e_1_3_2_6_2","first-page":"1043","year":"2001","unstructured":"Burke, D. S., and T. P. Monath. 2001. Flaviviruses, p. 1043-1126. In D. M. Knipe and P. M. Howley (ed.), Fields virology, 4th ed. Lippincott William & Wilkins, Philadelphia, Pa.","journal-title":"Fields virology"},{"key":"e_1_3_2_7_2","first-page":"1129","volume":"51","year":"2002","unstructured":"Centers for Disease Control and Prevention. 2002. Provisional surveillance summary of the West Nile virus epidemic-United States, January-November 2002. Morb. Mortal. Wkly. Rep.51:1129-1133.","journal-title":"Morb. Mortal. Wkly. Rep."},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.44.100190.003245"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.1.564-572.2000"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-3542(02)00185-7"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.111085598"},{"key":"e_1_3_2_12_2","first-page":"4599","year":"2005","unstructured":"Deas, T. S., I. Binduga-Gajewska, M. Tilgner, P. Ren, D. A. Stein, H. M. Moulton, P. L. Iversen, E. B. Kauffman, L. D. Kramer, and P.-Y. Shi. 2005. Inhibition of flavivirus infections by antisense oligomers specifically suppressing viral translation and RNA replication. J. Virol.4599-4609.","journal-title":"J. Virol."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2002.1685"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.11.2757"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.4.2034-2042.1993"},{"key":"e_1_3_2_16_2","unstructured":"J. Med. Chem."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.3.1343-1350.2005"},{"key":"e_1_3_2_18_2","first-page":"41","volume":"59","year":"2002","unstructured":"Hong, Z., and C. E. Cameron. 2002. Pleiotropic mechanisms of ribavirin antiviral activities. Prog. Drug Res.59:41-69.","journal-title":"Prog. Drug Res."},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.5.2788-2796.2005"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.21.13285-13297.2005"},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","first-page":"3606","DOI":"10.4049\/jimmunol.141.10.3606","volume":"141","year":"1988","unstructured":"Kimura-Kuroda, J., and K. Yasui. 1988. Protection of mice against Japanese encephalitis virus by passive administration with monoclonal antibodies. J. Immunol.141:3606-3610.","journal-title":"J. Immunol."},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.8.5116-5128.2005"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-74-4-733"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00660-8"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.10.4773-4784.2002"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M107360200"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.3.1943-1947.2005"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.3.1934-1942.2005"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.14.7804-7813.2003"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.18.10004-10014.2003"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.23.12901-12906.2003"},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.4049\/jimmunol.132.3.1533","volume":"132","year":"1984","unstructured":"Mathews, J. H., and J. T. Roehrig. 1984. Elucidation of the topography and determination of the protective epitopes on the E glycoprotein of Saint Louis encephalitis virus by passive transfer with monoclonal antibodies. J. Immunol.132:1533-1537.","journal-title":"J. Immunol."},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0042-6822(03)00341-6"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M305041200"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-3542(02)00013-X"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2335168100"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.16.9345"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1240"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.10.3944-3953.2004"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.12.4980-4988.2005"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008160123754"},{"key":"e_1_3_2_42_2","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1111\/j.1749-6632.2001.tb02704.x","volume":"951","year":"2001","unstructured":"Roehrig, J. T., L. A. Staudinger, A. R. Hunt, J. H. Mathews, and C. D. Blair. 2001. Antibody prophylaxis and therapy for flavivirus encephalitis infections. Ann. N. Y. Acad. Sci.951:286-297.","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06337.x"},{"key":"e_1_3_2_44_2","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.4049\/jimmunol.135.4.2805","volume":"135","year":"1985","unstructured":"Schlesinger, J. J., M. W. Brandriss, and E. E. Walsh. 1985. Protection against 17D yellow fever encephalitis in mice by passive transfer of monoclonal antibodies to the nonstructural glycoprotein gp48 and by active immunization with gp48. J. Immunol.135:2805-2809.","journal-title":"J. Immunol."},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2002.1453"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.12.5847-5856.2002"},{"key":"e_1_3_2_47_2","first-page":"759","volume":"7","year":"2001","unstructured":"Shimoni, Z., M. J. Niven, S. Pitlick, and S. Bulvik. 2001. Treatment of West Nile virus encephalitis with intravenous immunoglobulin. Emerg. Infect. Dis.7:759.","journal-title":"Emerg. Infect. Dis."},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1996.0067"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1997.8606"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(91)90440-M"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1993.1587"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.14.8698-8706.2005"},{"key":"e_1_3_2_53_2","unstructured":"World Health Organization. 2002. Dengue and dengue haemorrhagic fever. [Online.] http:\/\/www.who.int\/mediacentre\/factsheets\/fs117\/en\/ ."},{"key":"e_1_3_2_54_2","unstructured":"World Health Organization. 2002. Immunization vaccines and biologicals: Japanese encephalitis. [Online.] http:\/\/www.who.int\/vaccines-disease\/diseases\/je.shtml ."},{"key":"e_1_3_2_55_2","unstructured":"World Health Organization. 2001. Yellow fever. [Online.] http:\/\/www.who.int\/mediacentre\/factsheets\/fs100\/en\/ ."},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.8.3596-3604.2002"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm030277k"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.50.4.1320-1329.2006","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.50.4.1320-1329.2006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,3]],"date-time":"2024-02-03T13:57:35Z","timestamp":1706968655000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.50.4.1320-1329.2006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,4]]},"references-count":56,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2006,4]]}},"alternative-id":["10.1128\/AAC.50.4.1320-1329.2006"],"URL":"https:\/\/doi.org\/10.1128\/aac.50.4.1320-1329.2006","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,4]]},"assertion":[{"value":"2005-11-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-01-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-04-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}