Research ArticleVIRAL INFECTIONS

A direct-acting antiviral drug abrogates viremia in Zika virus–infected rhesus macaques

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Science Translational Medicine  10 Jun 2020:
Vol. 12, Issue 547, eaau9135
DOI: 10.1126/scitranslmed.aau9135

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An antiviral drug for Zika virus infection?

Zika virus infection causes severe disease in infants and adults. To date, no vaccine or treatment is available. In new work, Lim et al. conducted four studies in rhesus macaques to determine the safety and effectiveness of the antiviral drug galidesivir against Zika virus infection. The researchers infected 70 rhesus macaques with contemporary Zika virus isolates and tested galidesivir at various times after infection and at different drug doses. Galidesivir treatment of rhesus macaques was safe and offered protection against Zika virus infection. These data suggest the continued evaluation of galidesivir for treating Zika virus and similar viral infections.

Abstract

Zika virus infection in humans has been associated with serious reproductive and neurological complications. At present, no protective antiviral drug treatment is available. Here, we describe the testing and evaluation of the antiviral drug, galidesivir, against Zika virus infection in rhesus macaques. We conducted four preclinical studies in rhesus macaques to assess the safety, antiviral efficacy, and dosing strategies for galidesivir (BCX4430) against Zika virus infection. We treated 70 rhesus macaques infected by various routes with the Puerto Rico or Thai Zika virus isolates. We evaluated galidesivir administered as early as 90 min and as late as 72 hours after subcutaneous Zika virus infection and as late as 5 days after intravaginal infection. We evaluated the efficacy of a range of galidesivir doses with endpoints including Zika virus RNA in plasma, saliva, urine, and cerebrospinal fluid. Galidesivir dosing in rhesus macaques was safe and offered postexposure protection against Zika virus infection. Galidesivir exhibited favorable pharmacokinetics with no observed teratogenic effects in rats or rabbits at any dose tested. The antiviral efficacy of galidesivir observed in the blood and central nervous system of infected animals warrants continued evaluation of this compound for the treatment of flaviviral infections.

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