AsianScientist (May 6, 2016) – As our news feeds and social media accounts have been telling us, the Zika virus disease (Zika) that has reared its ugly head in Brazil is proving to be a particularly difficult nut to crack.
On February 1, 2016, the World Health Organization (WHO) declared the Zika outbreak a Public Health Emergency of International Concern, highlighting the need for more research into this poorly understood virus.
One thing we do know so far is that Zika is likely neurotrophic—it targets the brain and nervous system. While the widely-reported association between Zika and the birth defect, microcephaly, will take months to prove (or disprove), there is strong evidence that it is. Researchers attempting to recover the entire Zika virus genome from an aborted fetus with microcephaly also observed virus particles in the brain.
Now, we have another piece of the puzzle—and a particularly significant one, at that. Associate professor of the Emerging Infectious Diseases Programme at Duke-NUS Medical School in Singapore, Lok Shee-Mei, and colleagues have recently imaged the structure of Zika virus and identified potential sites on the virus to target with therapeutics. Their work, published in Nature, will prove essential to the development of a vaccine in the future.
Here, Lok tells Asian Scientist Magazine about the race against time to research a virus that is proving to be notoriously resilient.
- What is a flavivirus? What are some of the medically important diseases caused by flaviviruses?
Flavivirus is a virus that contains a single strand RNA genome, which is surrounded by a lipid membrane. There are two other proteins which are anchored on the membrane and is displayed on the outside of the virus particle. The medically important flaviviruses are Zika virus, dengue virus, Japanese encephalitis virus and West Nile virus.
- What was the main significance of your study?
That Zika virus is more thermally stable than dengue virus structure-wise, and it is consistent with its ability to stay infectious at extreme, feverish temperatures. We also identify that structural regions of the virus are related to its stability.
- How does the Zika virus structure explain the epidemiology of the current outbreak?
It does not explain the epidemiology of the current outbreak. The work suggests sites that can be targeted by drugs and antibodies so that we can lower the transmission rate and also possibly reduce the disease outcome.
- What was one major challenge that you faced while completing this study, and how did you overcome it?
There is tremendous competition in the field on this topic. One needs to work fast and at the same time, not sacrifice on the quality of the work. We have been working very hard, doing lots of overtime on the paper. Furthermore, all experiments have to be planned very well, as there is no time to repeat experiments if avoidable mistakes were made.
- How has your expertise in dengue research helped you in the course of this study?
Dengue is also a flavivirus; we are used to propagating this virus in tissue cultures. We also have a lot of experience with imaging dengue structures to high resolution. Zika virus behaves very similarly to dengue, so it is actually easier task to us to solve the structures compared to other groups who are new to this field. That definitely gives us a lot of advantage.
- Could you briefly explain how an antibody would work to destabilize the Zika virus structure?
The binding of antibody may be able to break some of the interactions on the surface of Zika virus to destabilize the structure. That will help reduce the infectivity or the lifespan of the virus.
- Besides understanding the effects of antibodies on the virus structure, what are some ways that worldwide efforts to control the Zika outbreak will benefit from your research?
The Zika virus structure can be used to design drugs and also will be used as a basis of vaccine design in the future.
The article can be found at: Kostyuchenko et al. (2016) Structure of the Thermally Stable Zika Virus.
Copyright: Asian Scientist Magazine; Photo: Duke-NUS Medical School.
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