Sofosbuvir inhibits yellow fever virus in vitro and in patients with acute liver failure

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art_MENDES_Sofosbuvir_inhibits_yellow_fever_virus_in_vitro_and_2019.PDF (1.9 MB)
Citações na Scopus
28
Tipo de produção
article
Data de publicação
2019
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER ESPANA
Autores
MENDES, Erica Araujo
PILGER, Denise Regina Bairros de
PASCOALINO, Bruno dos Santos
BALAN, Andrea
JR, Lucio Holanda Gondim de Freitas
DURIGON, Edison Luis
Citação
ANNALS OF HEPATOLOGY, v.18, n.6, p.816-824, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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.
Palavras-chave
Acute hepatitis, Flavivirus, YFV, Treatment, Antiviral
URI
https://observatorio.fm.usp.br/handle/OPI/34412
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MGT
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - IMT
Artigos e Materiais de Revistas Científicas - LIM/03
Artigos e Materiais de Revistas Científicas - LIM/07
Artigos e Materiais de Revistas Científicas - LIM/37
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