Most accurate picture of Zika yet creates potential for therapeutics

June 26, 2018

Researchers have created the most accurate picture of Zika to date, finding probable drug-binding pockets on the surface of the virus and paving the way for vaccine design.

Purdue researchers were the first to discover the structure of Zika virus in 2016. Using cryo-electron microscopy (cryo-EM), they created an image of the virus at a resolution of 3.8 Ångstrom, a unit used to express the size of atoms and molecules. Now, they've scaled that number down to 3.1, bringing them even closer to seeing atomic details of the virus. The findings were published in the journal Structure (Cell Press).

"This is the most accurate picture we have of the virus so far," said Michael Rossmann, the Hanley Distinguished Professor of Biological Sciences at Purdue. "These results will give us ways to efficiently design antiviral compounds and provide a basis for structure-based vaccine design."

The research team used new virus preparation methods and updated data processing techniques to get this improved resolution. The result of cryo-EM is an electron potential map, which can be interpreted by building an atomic model. The best fit between the model and the map is achieved using statistical adjustments known as "refinement."

"Our team extended and optimized the routine crystallographic refinement methods," Rossmann said.

Zika virus belongs to the family of flaviviruses that are transmitted by mosquitos and ticks. Rossmann's team compared the new Zika structure to other flaviviruses such as Dengue, West Nile and Japanese Encephalitis virus, which are structurally similar but cause different disease symptoms. Zika virus causes babies to be born with abnormally small heads and sometimes smaller brains, a condition known as microcephaly, and may result in Guillain-Barre syndrome in adults. Dengue Fever, on the other hand, causes flu-like symptoms and a skin rash.

"We compared the surface properties of these viruses and observed differences in the landscape of the surface exposed residues," said Madhu Sevvana, a postdoctoral researcher at Purdue and lead author of the paper. "We found certain structural differences on the surface, which could be a starting point for further mutational analyses."
-end-
The research team was advised by Rossmann and Richard Kuhn, the Trent and Judith Anderson Distinguished Professor in Science at Purdue. Researchers from Fudan University in China also contributed to this work. Funding was provided by the National Institutes of Health (grants AI076331 and AI07355).

Purdue University

Related Zika Virus Articles from Brightsurf:

'Domestication' increases mosquito's zika virus susceptibility
The Aedes aegypti aegypti subspecies of mosquito, which has become a ''domestic'' pest worldwide, can acquire and transmit Zika virus more easily than its African forerunner.

Greater mosquito susceptibility to Zika virus fueled the epidemic
By experimentally comparing wild populations of Ae. aegypti the researchers discovered that the invasive subspecies is very effective at transmitting the Zika virus not only because it has more frequent contacts with humans for blood meals, but also as a result of its greater susceptibility to the virus relative to the African subspecies.

Unravelling mother to baby transmission of Zika virus
Researchers have discovered that when a pregnant mother is infected by Zika virus, it can remain in the placenta for months, causing damage that can be dangerous to the fetus.

Consequences of Zika virus attack on glial cells
Few studies have identified the effects of zika virus infection on astrocytes, as well as their association with developmental alterations, including brain malformations and microcephaly.

Breakthrough in Zika virus vaccine
Researchers from the University of Adelaide have made significant advances in developing a novel vaccine against Zika virus, which could potentially lead to global elimination of the disease.

How the Zika virus can spread
The spread of infectious diseases such as Zika depends on many different factors.

Prior Zika virus or dengue virus infection does not affect secondary infections in monkeys
Previous infection with either Zika virus or dengue virus has no apparent effect on the clinical course of subsequent infection with the other virus, according to a study published August 1 in the open-access journal PLOS Pathogens by David O'Connor of the University of Wisconsin-Madison, and colleagues.

Early dengue virus infection could "defuse" zika virus
The Zika virus outbreak in Latin America has affected over 60 million people up to now.

Long-term consequences of Zika virus infection
Mice exposed to the Zika virus during later stages of gestation present behaviors reminiscent of attention-deficit/hyperactivity disorder, according to a study of genetically diverse animals.

Protection from Zika virus may lie in a protein derived from mosquitoes
By targeting a protein found in the saliva of mosquitoes that transmit Zika virus, Yale investigators reduced Zika infection in mice.

Read More: Zika Virus News and Zika Virus Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.