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

Antiviral Res. 2020 Oct:182:104859. doi: 10.1016/j.antiviral.2020.104859. Epub 2020 Jul 7.

Abstract

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.

Keywords: Congenital Zika virus syndrome; Pregnancy; Rhesus monkeys; Sofosbuvir; Zika virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use*
  • Brazil
  • Female
  • Infectious Disease Transmission, Vertical / prevention & control*
  • Macaca mulatta
  • Pregnancy
  • Pregnancy Complications, Infectious / prevention & control
  • Pregnancy Complications, Infectious / virology
  • Sofosbuvir / administration & dosage
  • Sofosbuvir / therapeutic use*
  • Translational Research, Biomedical
  • Viremia / drug therapy
  • Viremia / prevention & control
  • Zika Virus / drug effects*
  • Zika Virus / immunology
  • Zika Virus Infection / congenital
  • Zika Virus Infection / drug therapy
  • Zika Virus Infection / prevention & control*
  • Zika Virus Infection / transmission*

Substances

  • Antibodies, Viral
  • Antiviral Agents
  • Sofosbuvir