Abstract：
: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 × 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 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.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Ferreira AC,Zaverucha-do-Valle C,Reis PA,Barbosa-Lima G,Vieira YR,Mattos M,Silva PP,Sacramento C,de Castro Faria Neto HC,Campanati L,Tanuri A,Brüning K,Bozza FA,Bozza PT,Souza TMLdoi
10.1038/s41598-017-09797-8subject
Has Abstractpub_date
2017-08-25 00:00:00pages
9409issue
1issn
2045-2322pii
10.1038/s41598-017-09797-8journal_volume
7pub_type
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