{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:36:29Z","timestamp":1789540589605,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T00:00:00Z","timestamp":1517443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005363","name":"Universidad de Buenos Aires","doi-asserted-by":"publisher","award":["00404"],"award-info":[{"award-number":["00404"]}],"id":[{"id":"10.13039\/501100005363","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["3080"],"award-info":[{"award-number":["3080"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:sec><jats:label\/><jats:p>The aim of this study was to investigate the effect of A771726, the active metabolite of leflunomide, (CONICET\u2010UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad against the infection with Jun\u00edn virus (JUNV), agent of Argentine hemorrhagic fever (AHF). The treatment with non\u2010cytotoxic concentrations of A771726 of Vero and A549 cells infected with JUNV inhibited virus replication in a dose\u2010dependent manner, as determined by virus yield reduction assay. The antiviral effectiveness of A771726 was not importantly affected by the multiplicity of infection and the virus strain. Moreover, the combination of A771726 and ribavirin had a significantly more potent antiviral activity than each single drug treatment. Mechanistic studies showed that the main action of A771726 is exerted before 6\u2009h of JUNV infection. Accordingly, inhibition of viral RNA synthesis was detected in treated infected cells by real time RT\u2010PCR. The exogenous addition of uridine or orotic acid produced a partial reversal of the inhibitory effect of A771726 on infective virus production whereas a total reversion was detected on JUNV RNA synthesis, probably by restoration of the enzymatic activity of dihydroorotate dehydrogenase (DHODH) and the intracellular pyrimidine pools. In conclusion, these results suggest that the antiviral target would be viral RNA synthesis through pyrimidine depletion, but any other effect of the compound on JUNV infection cannot be excluded. This study opens the possibility of the therapeutic application of a wide spectrum host\u2010targeted compound alone or in combination with ribavirin to combat AHF as well as other human pathogenic arenaviruses.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmv.25024","type":"journal-article","created":{"date-parts":[[2018,1,10]],"date-time":"2018-01-10T00:52:33Z","timestamp":1515545553000},"page":"819-827","source":"Crossref","is-referenced-by-count":29,"title":["Antiviral activity of A771726, the active metabolite of leflunomide, against Jun\u00edn virus"],"prefix":"10.1002","volume":"90","author":[{"given":"Claudia S.","family":"Sep\u00falveda","sequence":"first","affiliation":[{"name":"Laboratorio de Virolog\u00eda, Departamento de Qu\u00edmica Biol\u00f3gica\u2010IQUIBICEN (CONICET\u2010UBA), Facultad de Ciencias Exactas y Naturales Universidad de Buenos Aires Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cybele 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