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Title: Sofosbuvir inhibits yellow fever virus in vitro and in patients with acute liver failure
Authors: MENDES, Erica AraujoPILGER, Denise Regina Bairros deNASTRI, Ana Catharina de Seixas SantosMALTA, Fernanda de MelloPASCOALINO, Bruno dos SantosD'ALBUQUERQUE, Luiz Augusto CarneiroBALAN, AndreaJR, Lucio Holanda Gondim de FreitasDURIGON, Edison LuisCARRILHO, Flair JosePINHO, Joao Renato Rebello
Citation: ANNALS OF HEPATOLOGY, v.18, n.6, p.816-824, 2019
Abstract: Introduction and objectives: Direct antiviral agents (DAAs) are very efficient in inhibiting hepatitis C virus and might be used to treat infections caused by other flaviviruses whose worldwide detection has recently increased. The aim of this study was to verify the efficacy of DAAs in inhibiting yellow fever virus (YFV) by using drug repositioning (a methodology applied in the pharmaceutical industry to identify new uses for approved drugs). Materials and methods: Three DAAs were evaluated: daclatasvir, sofosbuvir and ledipasvir or their combinations. For in vitro assays, the drugs were diluted in 100% dimethyl sulfoxide. Vaccine strain 17D and a 17D strain expressing the reporter fluorescent protein were used in the assays. A fast and reliable cell-based screening assay using Vero cells or Huh-7 cells (a hepatocyte-derived carcinoma ell line) was carried out. Two patients who acquired yellow fever virus with acute liver failure were treated with sofosbuvir for one week as a compassionate use. Results: Using a high-content screening assay, we verified that sofosbuvir presented the best antiviral activity against YFV. Moreover, after an off-label treatment with sofosbuvir, the two female patients diagnosed with yellow fever infection displayed a reduction in blood viremia and an improvement in the course of the disease, which was observed in the laboratory medical parameters related to disease evolution. Conclusions: Sofosbuvir may be used as an option for treatment against YFV until other drugs are identified and approved for human use. These results offer insights into the role of nonstructural protein 5 (NS5) in YFV inhibition and suggest that nonstructural proteins may be explored as drug targets for YFV treatment. (C) 2019 Fundacion Clinica Medica Sur, A.C.
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Artigos e Materiais de Revistas Científicas - FM/MGT
Departamento de Gastroenterologia - FM/MGT

Artigos e Materiais de Revistas Científicas - HC/ICHC
Instituto Central - HC/ICHC

Artigos e Materiais de Revistas Científicas - IMT
Instituto de Medicina Tropical - IMT

Artigos e Materiais de Revistas Científicas - LIM/03
LIM/03 - Laboratório de Medicina Laboratorial

Artigos e Materiais de Revistas Científicas - LIM/07
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental

Artigos e Materiais de Revistas Científicas - LIM/37
LIM/37 - Laboratório de Transplante e Cirurgia de Fígado

Artigos e Materiais de Revistas Científicas - ODS/03
ODS/03 - Saúde e bem-estar

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