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Blocking Zika virus vertical transmission.

Blocking Zika virus vertical transmission.
Author Information (click to view)

Mesci P, Macia A, Moore SM, Shiryaev SA, Pinto A, Huang CT, Tejwani L, Fernandes IR, Suarez NA, Kolar MJ, Montefusco S, Rosenberg SC, Herai RH, Cugola FR, Russo FB, Sheets N, Saghatelian A, Shresta S, Momper JD, Siqueira-Neto JL, Corbett KD, Beltrão-Braga PCB, Terskikh AV, Muotri AR,


Mesci P, Macia A, Moore SM, Shiryaev SA, Pinto A, Huang CT, Tejwani L, Fernandes IR, Suarez NA, Kolar MJ, Montefusco S, Rosenberg SC, Herai RH, Cugola FR, Russo FB, Sheets N, Saghatelian A, Shresta S, Momper JD, Siqueira-Neto JL, Corbett KD, Beltrão-Braga PCB, Terskikh AV, Muotri AR, (click to view)

Mesci P, Macia A, Moore SM, Shiryaev SA, Pinto A, Huang CT, Tejwani L, Fernandes IR, Suarez NA, Kolar MJ, Montefusco S, Rosenberg SC, Herai RH, Cugola FR, Russo FB, Sheets N, Saghatelian A, Shresta S, Momper JD, Siqueira-Neto JL, Corbett KD, Beltrão-Braga PCB, Terskikh AV, Muotri AR,

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Scientific reports 2018 01 198(1) 1218 doi 10.1038/s41598-018-19526-4
Abstract

The outbreak of the Zika virus (ZIKV) has been associated with increased incidence of congenital malformations. Although recent efforts have focused on vaccine development, treatments for infected individuals are needed urgently. Sofosbuvir (SOF), an FDA-approved nucleotide analog inhibitor of the Hepatitis C (HCV) RNA-dependent RNA polymerase (RdRp) was recently shown to be protective against ZIKV both in vitro and in vivo. Here, we show that SOF protected human neural progenitor cells (NPC) and 3D neurospheres from ZIKV infection-mediated cell death and importantly restored the antiviral immune response in NPCs. In vivo, SOF treatment post-infection (p.i.) decreased viral burden in an immunodeficient mouse model. Finally, we show for the first time that acute SOF treatment of pregnant dams p.i. was well-tolerated and prevented vertical transmission of the virus to the fetus. Taken together, our data confirmed SOF-mediated sparing of human neural cell types from ZIKV-mediated cell death in vitro and reduced viral burden in vivo in animal models of chronic infection and vertical transmission, strengthening the growing body of evidence for SOF anti-ZIKV activity.

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