Such rapid progress is remarkable, given that Zika came essentially out of nowhere, unlike Ebola, where a number of programs were ready for testing at the time of the most recent (deadly) outbreak (Nat. Biotechnol. 32, 849–850, 2014). Previous work on related flaviviruses like dengue and chikungunya, as well as existing infrastructure for creating and testing vaccines, has helped, of course. It was a “perfect storm” of capabilities and partnerships, says Nelson Michael, of Walter Reed Army Institute of Research (WRAIR) in Bethesda, Maryland, whose group collaborated with Dan Barouch, director of the Center of Virology and Vaccine Research at Beth Israel Hospital in Boston. At the outset, WRAIR already had a concentration in flavivirus experts, with work on yellow fever dating back to the 1890s, while Barouch's group, with expertise stemming from work on HIV vaccines, had the infrastructure to design and test immunogens. “What most groups take four years to do, we did in 180 days.” he says.
Although the Zika, a mosquito-borne flavivirus, has been around since the 1940s, it wasn't until late 2015 that the problems with fetal development in pregnant women infected with the virus emerged in the Americas. This captured the attention of researchers like Hengli Tang at Florida State University in Tallahassee, who had a small NIH-funded program on dengue. In January, when his group was preparing to make a large batch of dengue virus, he switched gears immediately to Zika. Between then and now, his group, in collaboration with neuroscientists Hongjun Song and Guo-Li Ming at Johns Hopkins University in Baltimore, and Wei Zheng, at NIH's National Center for Advancing Translational Sciences (NCATS), published a series of papers relating to the virus's effects on neuronal cells (neural progenitor cells, astrocytes and brain organoids developed from induced pluripotent stem cells) (Cell 165, 1238–1254, 2016). The team also identified small molecules that inhibit Zika virus replication from an NCATS repurposing library of 6,000 compounds (Nat. Med. 22, 1101–1107, 2016). Their hits fall into two categories, inhibitors of Zika infection in human central nervous system cells and inhibitors of Zika-induced caspase activity, which causes neuronal cell death.
This is a preview of subscription content, access via your institution