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

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.

• Authors: So-Yon Lim, Christa E Osuna, Katharine Best, Ray Taylor, Elsa Chen, Gyeol Yoon, Jessica L Kublin, Dane Schalk, Nancy Schultz-Darken, Saverio Capuano, David Safronetz, Ma Luo, Steve MacLennan, Amanda Mathis, Yarlagadda S Babu, William P Sheridan, Alan S Perelson, James B Whitney
• Journal: Science translational medicine (Sci Transl Med) Vol. 12 Issue 547 (06 10 2020) ISSN: 1946-6242 [Electronic] United States
• PMID: 32522808 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Chemical References

• Antiviral Agents

Topics

• Animals
• Antiviral Agents (therapeutic use)
• Hepatitis C, Chronic
• Macaca mulatta
• Rabbits
• Rats
• Viremia (drug therapy)
• Zika Virus
• Zika Virus Infection (drug therapy)