Drug screen identifies leads for Zika virus drug development

Compounds that suppress Zika virus replication or that prevent the death of cells infected by the virus are reported in a paper published online in Nature Medicine this week. These compounds - which include some drugs already approved to treat other human conditions - and their targets represent a starting point for anti-Zika drug development and preclinical studies.

Similarly to dengue virus and chikungunya virus, Zika virus can cause flu-like symptoms in some individuals. Unlike dengue virus and chikungunya virus, Zika virus infection can also result in the congenital defect microcephaly in developing fetuses, and in Guillain-Barre disease in adults. Hongjun Song, Guo-li Ming, Wei Zheng, Hengli Tang and colleagues screened a library of approximately 6,000 compounds that included US Food and Drug Administration (FDA)-approved drugs and experimental therapies currently in clinical trials, and identified two classes of compounds: one inhibits the death of cells infected by Zika virus and the other blocks Zika virus replication in infected cells.

The two classes of compounds identified showed activity in several relevant types of brain cells - including human neural progenitor cells (which contribute to the development of the brain cortex in the fetus) and astrocytes - and in 3D brain organoid cultures. The compounds also worked when given either before or after exposure to Zika virus. Finally, the two classes of compounds showed even greater benefits when used together than when given individually.

Further research is needed before these compounds can be considered for human treatment, especially of pregnant women. Essential next steps include testing the efficacy and safety of these lead compounds in animal models of adult and fetal Zika virus infection.

**This study is part of a group of papers that is free to access until further notice, per an agreement among publishers and research funders to ensure that the global response to public health emergencies is informed by the best available research evidence and data. A dedicated hub hosting all Springer Nature Zika content can be found here.**

doi: 10.1038/nm.4184

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