Suppression of Zika Virus Infection in the Brain by the Antiretroviral Drug Rilpivirine

Repurposing an HIV Drug for Zika Virus Therapy

“…Third, Sariyer et al 2 demonstrated the in vivo efficacy of rilpivirine in a ZIKV interferon a/ b receptor (IFNAR) À/À mouse (type I interferon receptor knockout) model ( Figure 1B). Treatment of ZIKV-infected IFNAR À/À mice with rilpivirine reduced organ viral burden and weight loss, improved clinical score, and prevented death.…”

“…Second, Sariyer et al 2 provided five lines of evidence to support that rilpivirine targets ZIKV RdRp ( Figure 1A). (1) 5) Overexpression of wild-type RdRp protein in ZIKV-infected cells, but not the 14-amino acid mutant protein, competed for rilpivirine binding and thus alleviated compound-mediated antiviral activity.…”

“…Zika virus (ZIKV) is a mosquito-borne flavivirus that can cause devastating microcephaly and other congenital syndromes in infants born to infected pregnant women as well as Guillain-Barré syndrome in infected adults. 1 In this issue of Molecular Therapy, Sariyer et al 2 present evidence demonstrating that rilpivirine, a US Food and Drug Administration (FDA)-approved HIV drug, inhibits ZIKV RNA-dependent RNA polymerase (RdRp), leading to potent anti-ZIKV activity in cell cultures and mice. The study highlights the potential of repurposing clinically approved drugs for possible prevention and treatment of ZIKV infection and its associated disease.…”

“…However, those inhibitors have low potency in cell culture, and their in vivo efficacy has not been reported. Taking the repurposing approach, Sariyer et al 2 have now identified an HIV drug, rilpivirine, as an anti-ZIKV inhibitor in both cell cultures and mouse models by blocking the viral RdRp ( Figure 1).…”

“…First, Sariyer et al 2 found that human primary astrocytes are more susceptible to ZIKV infection than several other human cell types, including fetal microglia, fetal neuron, and neural progenitor cells. Using ZIKV infection of astrocytes as a screening assay, they identified rilpivirine as a ZIKV inhibitor from eight FDA-approved HIV nucleoside and non-nucleoside reverse transcriptase drugs.…”