BCX4430, a Broad-Spectrum Adenosine Analog Direct-Acting Antiviral Drug, Abrogates Viremia in Rhesus Macaques Challenged With Zika Virus

Abstract

Methods. We conducted a pre-clinical study in rhesus monkeys to assess the safety and efficacy of BCX4430 against ZIKV infection. Fifteen animals were subcutaneously challenged with 1 × 105 TCID50 of a Puerto Rican ZIKV isolate. Animals were distributed into 3 groups (n = 5/group). Ninety minutes after challenge, group 1 received intramuscular (I.M.) doses of 100 mg/kg BCX4430 BID on Day 0 followed by 25 mg/kg BID for 9 additional days. Group 2 received only 100 mg/kg BCX4430 IM BID on Day 0. Group 3 received vehicle only. We followed multiple endpoints, including ZIKV RNA levels in plasma, urine, saliva, and cerebrospinal fluid. Immune activation, complete blood counts, chemistries and BCX4430 pharmacokinetics were longitudinally monitored throughout the study.