The research group who have achieved the breakthrough are led by Purdue University researchers. The primary aim was to pinpoint weaknesses with the viral structure that would make for effective anti-viral targets. There seems to have been some success.
In a research note, Richard Kuhn, director of the Purdue Institute for Inflammation, Immunology and Infectious Diseases, states in a research note: “The structure of the virus provides a map that shows potential regions of the virus that could be targeted by a therapeutic treatment.” One of the receptors targeted by Zika could be AXL, a protein crowded on the surface of neural stem cell.
The structure was revealed using cryo-electron microscopy. This provided the best resolution of the viral structure possible (previous methods were reliant upon X-ray crystallography.) The images show the virus to have a reveal a bumpy, golf ball‒shaped structure. Visualizing a virus with a lipid membrane, like Zika, is a complex and modifications to the imaging methods were required. The viral sample studied was taken from a patient infected during the French Polynesia epidemic.
The virus has an RNA genome surrounded by a lipid, or fatty, membrane inside an icosahedral protein shell. What is important, in terms of drug development, is its structure. The viral structure was revealed to be 3.8Å. The image revealed the atomic structure, made from specific chemical entities, including 20 naturally occurring amino acids.
Despite being first detected in Nigeria in 1947, little is known about the Zika virus (which is transmitted to people via mosquitoes.) This paucity of knowledge is reflective of the virus, until 2015, not being regarded as significant. It was known to infect only a low number of people, and with most, the symptoms are asymptomatic. For the one in four who are infected, the disease manifests as a mild fever, lasting only seven days. However, with the Brazil outbreak more serious medical issues arise, including microcephaly and Guillain-Barré syndrome, a rapid-onset muscle weakness. The disease has been reported in 33 countries to date, leading the World Health Organization to declare a public health emergency.
Importantly, the researchers identified regions within the Zika virus structure that are different to other flaviviruses (this is the family group for the Zika virus — the family includes other viruses of concern, such as dengue, West Nile, yellow fever, Japanese encephalitis and tick-borne encephalitic viruses.) Flavivirus structures differ in the amino acids that form the viral shell, and it was here the cryo-electron microscopy allowed the researchers to distinguish Zika from other viruses in the family.
The new research is published in the journal Science. The research paper is titled “The 3.8Å resolution cryo-EM structure of Zika Virus.”
