For the first time ever, scientists from Purdue University have managed to determine the structure of the Zika virus, revealing insights that are crucial in the development of treatments and vaccines. Furthermore, the team was able to pinpoint regions within the virus' structure that differ from other viruses in the flavivirus family, such as West Nile, yellow fever and dengue.
"The structure of the virus provides a map that shows potential regions of the virus that could be targeted by a therapeutic treatment, used to create an effective vaccine or to improve our ability to diagnose and distinguish Zika infection from that of other related viruses," said Richard Kuhn, who led the study. "Determining the structure greatly advances our understanding of Zika - a virus about which little is known. It illuminates the most promising areas for further testing and research to combat infection."
The team examined a strain of the virus from a patient infected during the French Polynesia epidemic. It determined the structure to 3.8Å, a near-atomic resolution that revealed key features of the virus' structure, allowing it to view groups of atoms and recognize the chemical entities that they form.
Upon analysis, the team found that the structure was very similar to that of other flaviviruses, possessing an RNA genome contained in a lipid membrane located inside of an icosahedral protein shell. However, subtle differences are the key to determining effective treatments.
"Most viruses don't invade the nervous system or the developing fetus due to blood-brain and placental barriers, but the association with improper brain development in fetuses suggest Zika does," said Devika Sirohi, co-author of the study. "It is not clear how Zika gains access to these cells and infects them, but these areas of structural difference may be involved. These unique areas may be crucial and warrant further investigation."
In addition, the team discovered that all flavivirus structures differ in terms of the amino acids that surround a glycosylation site in the virus shell. In the Zika virus, the site that differs extends from the surface of the virus, and a carbohydrate molecule is attached to the viral protein at this location.
Most viruses that project glycosylation sites outwards take advantage of an attachment receptor molecule on the surface of human cells, which causes it to recognize the sugars and bind to them. The different amino acids in this mechanism could help scientists determine the kinds of molecules that Zika can attach to and the different human cells that it can infect.
"If this site functions as it does in dengue and is involved in attachment to human cells, it could be a good spot to target an antiviral compound," said Michael Rossmann, who led the research team along with Kuhn. "If this is the case, perhaps an inhibitor could be designed to block this function and keep the virus from attaching to and infecting human cells."
The findings were published in the March 31 issue of Science.
