Article
Yellow fever virus is susceptible to sofosbuvir both in vitro and in vivo
Registro en:
FREITAS, Caroline S. de et al. Yellow fever virus is susceptible to sofosbuvir both in vitro and in vivo. Plos Neglected Tropical Diseases, p. 1-22, 30 Jan. 2019.
1935-2727
10.1371/journal.pntd.0007072
Autor
Freitas, Caroline S. de
Higa, Luiza M.
Sacramento, Carolina Q.
Ferreira, André C.
Reis, Patricia Alves
Delvecchio, Rodrigo
Monteiro, Fábio Luís Lima
Barbosa-Lima, Giselle
Westgarth, Harrison James
Vieira, Yasmine Rangel
Mattos, Mayara
Rocha, Natasha
Hoelz, Lucas Villas Bôas
Leme, Rennan Papaleo Paes
Bastos, Mônica M.
Rodrigues, Gisele Olinto L.
Lopes, Carla Elizabeth M.
Queiroz Junior, Celso Martins
Lima, Cristiano X.
Costa, Vivian V.
Teixeira, Mauro M.
Bozza, Fernando A.
Bozza, Patrícia Torres
Boechat, Nubia
Tanuri, Amilcar
Souza, Thiago Moreno L.
Resumen
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.