Cracking Zika’s code

Michael Rossmann, who was the first to map the common cold virus at an atomic level, is a pioneer in using supercomputers to reveal the structure of viruses. Richard Kuhn, who teamed up with Rossmann to determine the structure of the West Nile virus, is an international expert in flaviviruses such as dengue, West Nile and chikungunya.

Together, these researchers and their collaborators, postdoctoral scientists and graduate students became the first in the world to crack the code of another flavivirus, Zika. And they did it in just a few short months, providing timely insights for the development of  effective antiviral treatments and vaccines against the mosquito-borne illness, which has already infected thousands on multiple continents and led to the birth defect microcephaly among some babies born to infected mothers.

“Getting the structure puts us in a good position to find a drug against the virus,” says Rossmann, the Hanley Professor of Biological Sciences.

The researchers began their marathon in fall 2015, acquiring samples from the Zika outbreak in French Polynesia. After being purified, frozen and placed on grids, the samples were ready for microscopic analysis. Using a new direct counting electron detector that attaches to the university’s electron microscope in Hockmeyer Hall, the researchers generated hundreds of thousands of images of the virus from various orientations. Then, after analyzing data sets with Purdue’s supercomputers, the researchers worked day and night to turn individual projections into a 3-D representation that was officially revealed last March.

Illnesses like Zika — which is transmitted via mosquitoes like the Aedes aegypti — have a devastating domino effect; as more people get infected, more mosquitoes pass the disease on to other people, ultimately cascading into large-scale outbreaks. The association with birth defects brings great urgency for new strategies to contain its spread.

“Knowing the structure provides a huge platform for us to begin to do new experiments,” says Kuhn, former head of Purdue’s Department of Biological Sciences and director of the Purdue Institute of Inflammation, Immunology and Infectious Diseases (PI4D).

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