Sofosbuvir protects Zika virus-infected mice from mortality, preventing short- and long-term sequelae

• Published in: Scientific reports 2017-08, Vol.7 (1), p.9409-9, Article 9409
• Main Authors: Ferreira, André C., Zaverucha-do-Valle, Camila, Reis, Patrícia A., Barbosa-Lima, Giselle, Vieira, Yasmine Rangel, Mattos, Mayara, Silva, Priscila de Paiva, Sacramento, Carolina, de Castro Faria Neto, Hugo C., Campanati, Loraine, Tanuri, Amilcar, Brüning, Karin, Bozza, Fernando A., Bozza, Patrícia T., Souza, Thiago Moreno L.
• Format: Article
• Language: English
• Subjects: 45; 45/77; 631/154/436; 631/326/596/1296; 64; 64/60; Amygdala; Animals; Animals, Newborn; Antiviral agents; Antiviral Agents - administration & dosage; Antiviral Agents - pharmacology; Antiviral drugs; Cercopithecus aethiops; Complications; Congenital defects; Flavivirus; Hepatitis C; Hippocampus; Humanities and Social Sciences; Kidneys; Memory; Mice; multidisciplinary; Neonates; Neurological diseases; Public health; Reflex, Righting; RNA, Viral; Science; Science (multidisciplinary); Sofosbuvir - administration & dosage; Sofosbuvir - pharmacology; Spleen; Vector-borne diseases; Vero Cells; Virus Replication - drug effects; Zika virus; Zika Virus - physiology; Zika Virus Infection - drug therapy; Zika Virus Infection - mortality
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-09797-8

Zika virus (ZIKV) causes significant public health concerns because of its association with congenital malformations, neurological disorders in adults, and, more recently, death. Considering the necessity to mitigate ZIKV-associated diseases, antiviral interventions 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 × 10 7 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 the blood plasma, spleen, kidney, and brain. Early treatment with sofosbuvir doubled the percentage and time of survival of ZIKV-infected animals. Sofosbuvir also prevented the acute neuromotor impairment triggered by ZIKV. In the long-term behavioural analysis of ZIKV-associated sequelae, sofosbuvir prevented loss of hippocampal- and amygdala-dependent memory. Our results indicate that sofosbuvir inhibits ZIKV replication in vivo , which is consistent with the prospective necessity of antiviral drugs to treat ZIKV-infected individuals.