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

2020; Elsevier BV; Volume: 182; Linguagem: Inglês

10.1016/j.antiviral.2020.104859

1872-9096

Noemi Rovaris Gardinali, Renato Sérgio Marchevsky, Jaqueline Mendes de Oliveira, Marcelo Pelajo‐Machado, Tatiana Kugelmeier, Marcio P. Castro, Aline C. A. Silva, Douglas Pereira Pinto, Laís Bastos da Fonseca, Leandro Schiavo Vilhena, Heliana Martins Pereira, Sheila Maria Barbosa de Lima, Emily Hime Miranda, Gisela Freitas Trindade, José Linhares, Stephanie A. Silva, Juliana Gil Melgaço, Ada M. B. Alves, Julio Morán, Maria C.C. Silva, Rômulo José Soares‐Bezerra, Andreza Soriano, Gentil Arthur Lins Bentes Mendonça de Vasconcelos, Fernanda O. Bottino, Sarah Beatriz Salvador Castro Faria, Rafael F. Nudelman, Claudia A.A. Lopes, Javier A.S. Perea, Klena Sarges, Márcia Cristina Ribeiro Andrade, Marcia Motta, Marcos S. Freire, Thiago Moreno L. Souza, Jonas Schmidt‐Chanasit, Marcelo Alves Pinto,

Virology and Viral Diseases

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.