Sofosbuvir shows a protective effect against vertical transmission of Zika virus and the associated congenital syndrome in rhesus monkeys.

Gardinali, Noemi R; Marchevsky, Renato S; Oliveira, Jaqueline M; Pelajo-Machado, Marcelo; Kugelmeier, Tatiana; Castro, Marcio P; Silva, Aline C A; Pinto, Douglas P; Fonseca, Lais B; Vilhena, Leandro S; Pereira, Heliana M; Lima, Sheila M B; Miranda, Emily H; Trindade, Gisela F; Linhares, José H R; Silva, Stephanie A; Melgaco, Juliana Gil; Alves, Ada M B; Moran, Julio; Silva, Maria C C; Soares-Bezerra, Rômulo J; Soriano, Andreza; Bentes, Gentil A; de Oliveira Bottino, Fernanda; Salvador Castro Faria, Sarah Beatriz; Nudelman, Rafael F; Lopes, Claudia A A; Perea, Javier A S; Sarges, Klena; Andrade, Márcia C R; Motta, Márcia C V A; Freire, Marcos S; Souza, Thiago M L; Schmidt-Chanasit, Jonas; Pinto, Marcelo A

The outbreaks of Zika virus (ZIKV) infection in Brazil, 2015-2016, were associated with severe congenital malformations. Our translational study aimed to test the efficacy of the antiviral agent sofosbuvir (SOF) against vertical transmission of ZIKV and the associated congenital syndrome (CZS), using a rhesus monkey model. Eight pregnant macaques were successfully infected during the organogenesis phase with a Brazilian ZIKV strain; five of them received SOF from two to fifteen days post-infection. Both groups of dams showed ZIKV-associated clinical signals, detectable ZIKV RNA in several specimens, specific anti-ZIKV IgM and IgG antibodies, and maternal neutralizing antibodies. However, malformations occurred only among non-treated dam offspring. Compared to non-treated animals, all SOF-treated dams had a shorter ZIKV viremia and four of five neonates had undetectable ZIKV RNA in blood and tissue samples. These results support further clinical evaluations aiming for the prevention of CZS.