{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:01:42Z","timestamp":1792440102973,"version":"4.5.0"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2011,2,1]],"date-time":"2011-02-01T00:00:00Z","timestamp":1296518400000},"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":[[2011,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>A number of New World arenaviruses (Juni\u0301n [JUNV], Machupo [MACV], and Guanarito [GTOV] viruses) can cause human disease ranging from mild febrile illness to a severe and often fatal hemorrhagic fever syndrome. These highly pathogenic viruses and the Old World Lassa fever virus pose a significant threat to public health and national security. The only licensed antiviral agent with activity against these viruses, ribavirin, has had mixed success in treating severe arenaviral disease and is associated with significant toxicities. A novel pyrazine derivative currently in clinical trials for the treatment of influenza virus infections, T-705 (favipiravir), has demonstrated broad-spectrum activity against a number of RNA viruses, including arenaviruses. T-705 has also been shown to be effective against Pichinde arenavirus infection in a hamster model. Here, we demonstrate the robust antiviral activity of T-705 against authentic highly pathogenic arenaviruses in cell culture. We show that T-705 disrupts an early or intermediate stage in viral replication, distinct from absorption or release, and that its antiviral activity in cell culture is reversed by the addition of purine bases and nucleosides, but not with pyrimidines. Specific inhibition of viral replication\/transcription by T-705 was demonstrated using a lymphocytic choriomeningitis arenavirus replicon system. Our findings indicate that T-705 acts to inhibit arenavirus replication\/transcription and may directly target the viral RNA-dependent RNA polymerase.<\/jats:p>","DOI":"10.1128\/aac.01219-10","type":"journal-article","created":{"date-parts":[[2010,11,30]],"date-time":"2010-11-30T09:45:25Z","timestamp":1291110325000},"page":"782-787","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":113,"title":["T-705 (Favipiravir) Inhibition of Arenavirus Replication in Cell Culture"],"prefix":"10.1128","volume":"55","author":[{"given":"Michelle","family":"Mendenhall","sequence":"first","affiliation":[{"name":"Institute for Antiviral Research and Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Russell","sequence":"additional","affiliation":[{"name":"Institute for Antiviral Research and Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry","family":"Juelich","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily L.","family":"Messina","sequence":"additional","affiliation":[{"name":"Montana Biotechnology Center, The University of Montana, Missoula, Montana"},{"name":"Division of Biological Sciences, The University of Montana, Missoula, Montana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald F.","family":"Smee","sequence":"additional","affiliation":[{"name":"Institute for Antiviral Research and Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander N.","family":"Freiberg","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Holbrook","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousuke","family":"Furuta","sequence":"additional","affiliation":[{"name":"Research Laboratories, Toyama Chemical Company, Ltd., Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan-Carlos","family":"de la Torre","sequence":"additional","affiliation":[{"name":"Viral Immunobiology Laboratory, Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack H.","family":"Nunberg","sequence":"additional","affiliation":[{"name":"Montana Biotechnology Center, The University of Montana, Missoula, Montana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian B.","family":"Gowen","sequence":"additional","affiliation":[{"name":"Institute for Antiviral Research and Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1187816"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.18.2391"},{"key":"e_1_3_3_4_2","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1177\/135965359900400404","volume":"4","year":"1999","unstructured":"Chapman, L. E., et al. 1999. Intravenous ribavirin for hantavirus pulmonary syndrome: safety and tolerance during 1 year of open-label experience. Ribavirin Study Group. Antivir. Ther. 4:211-219.","journal-title":"Ribavirin Study Group. Antivir. Ther."},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2007.10.010"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0600652103"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.4.977-981.2002"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.3.981-986.2005"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2009.02.198"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1142"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003725"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00356-07"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2009.10.015"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01074-08"},{"key":"e_1_3_3_15_2","unstructured":"Reference deleted."},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2007.11.003"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909603107"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.8.3470-3477.2000"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.12.6393-6397.2002"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2008.07.009"},{"key":"e_1_3_3_21_2","unstructured":"The counter-bioterrorism research agenda of the National Institute of Allergy and Infectious Diseases (NIAID) for CDC category A agents. 2002"},{"key":"e_1_3_3_22_2","first-page":"493","volume":"27","year":"1938","unstructured":"Reed, L. J., and H. Muench. 1938. A simple method of estimating fifty percent endpoints. Am. J. Hyg. (Lond.) 27:493-497.","journal-title":"Am. J. Hyg. (Lond.)"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2008.09.007"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2006.01.012"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01051-06"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01739-09"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp274"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2.8.1317"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.70.4.1174"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0065-2571(92)90008-N"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01219-10","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01219-10","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T09:37:05Z","timestamp":1685871425000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01219-10"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,2]]},"references-count":29,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2011,2]]}},"alternative-id":["10.1128\/AAC.01219-10"],"URL":"https:\/\/doi.org\/10.1128\/aac.01219-10","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,2]]},"assertion":[{"value":"2010-09-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-11-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-01-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}