Small Molecules and Antibodies for Zika Therapy

Zika virus (ZIKV) infection during pregnancy can cause devastating congenital abnormities or fetal demise. Zika virus infection could also cause Guillain-Barré syndrome in adults. Mosquito control, vaccine, and therapeutics are 3 potential, effective means to prevent ZIKV infection. Here we review the current status of ZIKV drug discovery. Both small molecule inhibitors and therapeutic antibodies have been identified, some of which have shown promising efficacy in mouse models. Most inhibitors were identified through screening US Food and Drug Administration-approved drugs and clinical trial compounds; however, none of them were potent enough to justify a ZIKV clinical trial. Such a repurposing approach has also been pursued for dengue therapy, with several compounds tested in clinical trials showing no clinical benefits. Because pregnant women are the main target population for ZIKV treatment, therapeutic candidates could be developed through a 2-stage path. The first stage should demonstrate safety and efficacy in nonpregnant patients. Once efficacy has been demonstrated in nonpregnant patients, the candidates should be rapidly advanced to stage 2 for safety and efficacy evaluation in pregnant patients. The 2-stage developmental path is supported by previous results from trials with other viral infections that showed that treatment of pregnant women with antiviral drugs or hyperimmunoglobulins significantly reduced congenital abnormalities in neonates.