RT Journal Article
SR Electronic
T1 Sofosbuvir protects Zika virus-infected mice from mortality, preventing short- and long-term sequela
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 129197
DO 10.1101/129197
A1 André C. Ferreira
A1 Camila Z. Valle
A1 Patricia A. Reis
A1 Giselle Barbosa-Lima
A1 Yasmine Rangel Vieira
A1 Mayara Mattos
A1 Priscila de Paiva Silva
A1 Carolina Sacramento
A1 Hugo C. de Castro Faria Neto
A1 Loraine Campanati
A1 Amilcar Tanuri
A1 Karin Brüning
A1 Fernando A. Bozza
A1 Patrícia T. Bozza
A1 Thiago Moreno L. Souza
YR 2017
UL http://biorxiv.org/content/early/2017/04/20/129197.abstract
AB Zika virus (ZIKV) caused significant public health concern, because of its association with congenital malformations, neurological disorders in adults and, more recently, with deaths. Considering the necessity to mitigate the cases ZIKV-associated diseases, antiviral interventions against this virus are an urgent necessity. Sofosbuvir, a drug in clinical use against Hepatitis C Virus (HCV), is among the FDA-approved substances endowed with anti-ZIKV activity. In this work, we further investigated the in vivo activity of sofosbuvir against ZIKV. Neonatal Swiss mice were infected with ZIKV (2 x 107 PFU) and treated with sofosbuvir at 20 mg/kg/day, a concentration compatible with pre-clinical development of this drug. We found that sofosbuvir reduced acute levels of ZIKV from 60 to 90 % in different anatomical compartments, such as in blood plasma, spleen, kidney and brain. Early treatment with sofosbuvir doubled the percentage and time of survival of ZIKV-infected animals, despite the aggressive virus challenge assayed and also prevented the acute neuromotor impairment triggered by the virus. On the long-term behavior analysis of ZIKV-associated sequelae, sofosbuvir prevented loss of hippocampal- and amygdala-dependent memory. Our results point out that sofosbuvir inhibits ZIKV replication in vivo, which is consistent with the prospective necessity of antiviral drugs to treat ZIKV-infected individuals.