Researchers from Purdue University were able to determine the Zika virus structure in a new study. This discovery is crucial in identifying its weak spots essential for drug development.
The study highlighted the structure of Zika virus and how it differs from other types of flaviviruses such as yellow fever, dengue, Japanese encephalitis, West Nile, and tick-borne encephalitic viruses. The virus is associated with increased incidence of Guillain-Barre Syndrome (GBS) and microcephaly in infants born to mothers with Zika virus.
The mosquito-borne disease, according to the latest data by the Centers for Disease Control and Prevention (CDC), has caused about 312 travel-associated cases in the U.S., with one patient having GBS.
According to Richard Kuhn, Purdue Institute for Inflammation, Immunology and Infectious Diseases (PI4D) director, the differences in disease transmission and manifestation can be explained in the regions of the virus structure. These regions allowed Kuhn and his partner, Michael Rossman, Purdue's Hanley Distinguished Professor of Biological Sciences, to have a better understanding of the virus, highlighting areas for further testing and research.
Virus structure identification is quite difficult and time-consuming to do because Zika has a lipid membrane and does not readily organize in a crystal. To address this problem, the researchers used cryo-electron microscopy to visualize the structure in its more native state.
A strain of Zika virus from an infected patient from French Polynesia was isolated and identified in the structure to 3.8 angstrom. The level of the resolution allowed the researches to identify key features of the structure along with the groups of atoms that make up specific chemical entities similar to those that characterize one of the 20 naturally occurring amino acids.
As expected, the Zika virus is similar to those of other flaviviruses. It has a lipid membrane that surrounds its RNA genome within its icosahedral protein covering.
"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 Kuhn.
What the researchers found in their study can help in quickly addressing the growing concern for the disease. The structure similarity with other known flaviviruses may help in vaccine development, but researchers were quick to point out that significant structural differences may provide possible key concerns.
Zika virus structure revealed that the virus has a glycosylation site that is protruding from the virus surface, which has a carbohydrate molecule made up of various sugars. Kuhn compared this outward protrusion to a stranger offering a sweet treat to an unsuspecting victim. Human cells bind to the sugar and they eventually become infected.
"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," Rossmann said. "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 team is planning to conduct more tests using isolates from different regions of the Zika virus structure to offer a deeper insight on the virus.
"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, one of the study's research associates.
Sirohi added that further studies focusing on how the virus can gain access to the cell and eventually infect it are needed.
Since Zika virus has affected more than 33 countries, it has become a global concern that needs immediate course of action. Treatment plans including vaccine development would hugely benefit from this study.
The CDC recently released a guideline detailing pregnancy planning and recommendations for patients exposed to or infected with Zika virus.
