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PLoS Negl Trop Dis. 2019 Jan 30;13(1):e0007072. doi: 10.1371/journal.pntd.0007072. eCollection 2019 Jan.

Yellow fever virus is susceptible to sofosbuvir both in vitro and in vivo.

Author information

1
Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.
2
National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil.
3
Laboratório de Virologia Molecular, Instituto de Biologia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.
4
Instituto Nacional de Infectologia (INI), Fiocruz, Rio de Janeiro, RJ, Brazil.
5
Instituto de Tecnologia de Fármacos (Farmanguinhos), Fiocruz, Rio de Janeiro, RJ, Brazil.
6
Center for Research and Development of Pharmaceuticals, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil.
7
Research Group in Arboviral Diseases, Department of Morphology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil.
8
Cardiac Lab, Department of Morphology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil.
9
Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
10
Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil.

Abstract

Yellow fever virus (YFV) is a member of the Flaviviridae family. In Brazil, yellow fever (YF) cases have increased dramatically in sylvatic areas neighboring urban zones in the last few years. Because of the high lethality rates associated with infection and absence of any antiviral treatments, it is essential to identify therapeutic options to respond to YFV outbreaks. Repurposing of clinically approved drugs represents the fastest alternative to discover antivirals for public health emergencies. Other Flaviviruses, such as Zika (ZIKV) and dengue (DENV) viruses, are susceptible to sofosbuvir, a clinically approved drug against hepatitis C virus (HCV). Our data showed that sofosbuvir docks onto YFV RNA polymerase using conserved amino acid residues for nucleotide binding. This drug inhibited the replication of both vaccine and wild-type strains of YFV on human hepatoma cells, with EC50 values around 5 μM. Sofosbuvir protected YFV-infected neonatal Swiss mice and adult type I interferon receptor knockout mice (A129-/-) from mortality and weight loss. Because of its safety profile in humans and significant antiviral effects in vitro and in mice, Sofosbuvir may represent a novel therapeutic option for the treatment of YF. Key-words: Yellow fever virus; Yellow fever, antiviral; sofosbuvir.

PMID:
30699122
PMCID:
PMC6375661
DOI:
10.1371/journal.pntd.0007072
[Indexed for MEDLINE]
Free PMC Article

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