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.

人的寨卡病毒感染已与严重的生殖和神经系统并发症相关。目前，尚无保护性抗病毒药物治疗。在这里，我们描述了针对恒河猴中寨卡病毒感染的抗病毒药物加利地韦的测试和评估。我们在恒河猴中进行了四项临床前研究，以评估加利西韦（BCX4430）对寨卡病毒感染的安全性，抗病毒效力和给药策略。我们用波多黎各或泰国寨卡病毒分离株治疗了70条被各种途径感染的恒河猴。我们评估了加利地韦最早于皮下注射寨卡病毒感染后90分钟和迟至72小时，以及阴道内感染后5天的给药时间。我们评估了一系列加利地韦剂量的有效性，其终点包括血浆，唾液，尿液和脑脊髓液中的寨卡病毒RNA。加利地韦在猕猴中给药是安全的，并提供了暴露后预防寨卡病毒感染的保护措施。在任何测试剂量下，加利地韦在大鼠或兔子中均显示出良好的药代动力学，没有观察到致畸作用。在受感染动物的血液和中枢神经系统中观察到的加利地韦的抗病毒功效值得继续评估该化合物治疗黄病毒的感染。在任何测试剂量下，加利地韦在大鼠或兔子中均显示出良好的药代动力学，没有观察到致畸作用。在受感染动物的血液和中枢神经系统中观察到的加利地韦的抗病毒功效值得继续评估该化合物治疗黄病毒的感染。在任何测试剂量下，加利地韦在大鼠或兔子中均显示出良好的药代动力学，没有观察到致畸作用。在受感染动物的血液和中枢神经系统中观察到的加利地韦的抗病毒功效值得继续评估该化合物治疗黄病毒的感染。