PT  - JOURNAL ARTICLE
AU  - André C. Ferreira
AU  - Camila Z. Valle
AU  - Patricia A. Reis
AU  - Giselle Barbosa-Lima
AU  - Yasmine Rangel Vieira
AU  - Mayara Mattos
AU  - Priscila de Paiva Silva
AU  - Carolina Sacramento
AU  - Hugo C. de Castro Faria Neto
AU  - Loraine Campanati
AU  - Amilcar Tanuri
AU  - Karin Brüning
AU  - Fernando A. Bozza
AU  - Patrícia T. Bozza
AU  - Thiago Moreno L. Souza
TI  - Sofosbuvir protects Zika virus-infected mice from mortality, preventing short- and long-term sequela
AID  - 10.1101/129197
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 129197
4099  - http://biorxiv.org/content/early/2017/04/20/129197.short
4100  - http://biorxiv.org/content/early/2017/04/20/129197.full
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.