Purdue graduate student Devika Sirohi is part of the research team that determined the Zika virus structure. | Purdue University/ Mark Simons
A new study reveals the molecular structure of the Zika virus, which could help researchers develop vaccines and antivirals to combat the virus. The paper is published online and is available for free in the 1 April issue of Science. (Science has made the paper available as part of its commitment to share data relevant to public health emergencies.)
The ongoing Zika virus epidemic is of grave concern because of apparent links to congenital microcephaly, a medical condition in which the brain does not develop properly, resulting in a smaller than normal head, as well as Guillain Barré syndrome, a rare disorder in which the immune system attacks the nervous system causing severe muscle weakness and pain.
Zika belongs to a family of viruses called flaviviruses, which Richard Kuhn of Purdue University and some of his colleagues have been studying for more than a decade. "In the late fall it was clear that Zika was becoming an explosive epidemic with significant consequences, especially for women who were or might become pregnant," Kuhn said. "Since Zika is in the same family as West Nile and dengue viruses, it was an obvious next step for us to start working with the virus and prepare some high quality particles that we could analyze for structure."
He noted that one of the most challenging aspects is extracting virus particles of sufficient quality to analyze. "We've done it in a fairly rapid time," said Kuhn. "It was really a compressed operation in terms of getting the virus, growing it in large enough amounts, purifying it, getting a virus that is good enough to use in the microscope."
Once they had sufficient samples, the researchers used cryo-electron microscopy to analyze the structure. "Once we can see how the virus is put together, we can begin to understand how your immune system approaches that virus. What are the surface features of the virus that the immune system will hook onto?" explained Kuhn, noting that the structure of the virus is like a blueprint, and will serve as a starting point for targeting new antivirals or designing new vaccines.
Richard Kuhn discusses the importance of viral structure in designing antiviral treatments. | Purdue University/ Ted Schellenberger
Antibodies are markers that our immune system uses to identify and help remove foreign agents, such as viruses and bacteria. The analysis by Kuhn and colleagues reveals that Zika's structure is very similar to that of other flaviviruses, and particularly similar to dengue. However, Zika appears to have a slightly different structure in the regions where antibodies bind, and where the virus binds to host cells. These regions may be important in Zika virus attachment, entry, and disease progression.
Michael Rossmann of Purdue University, another researcher on the team, said they identified several potential sites where neutralizing antibodies may bind, which could be used to create a vaccine to prevent the spread of Zika. As well, he notes that there were possible targets for antiviral compounds, which could be used to treat people once they are infected.
Although knowing the structure of the virus is an important first step towards vaccines and antivirals, much more research is needed before these treatments could be given to people. Next, Rossmann, Kuhn, and their colleagues plan to explore Zika virus as it interacts with neutralizing antibodies and antiviral compounds, in the hopes of finding one that can bind to the virus and interfere with it.