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

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. Sofosbuv...

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Bibliographic Details
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:
Amygdala
Animals
Animals, Newborn
Antiviral agents
Antiviral Agents - administration & dosage
Antiviral Agents - pharmacology
Antiviral drugs
Cercopithecus aethiops
Complications
Congenital defects
Flavivirus
Hepatitis C
Hippocampus
Kidneys
Memory
Mice
Neonates
Neurological diseases
Public health
Reflex, Righting
RNA, Viral
Sofosbuvir - administration & dosage
Sofosbuvir - pharmacology
Spleen
Vero Cells
Virus Replication - drug effects
Zika virus
Zika Virus - physiology
Zika Virus Infection - drug therapy
Zika Virus Infection - mortality
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Summary: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 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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-09797-8