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September 13, 2016

A structured approach to combating Zika virus

By Abhijit Parkhe, Product Manager, Lab-scale Chromatography Systems, GE

In this post, Abhijit shares some news about a Zika virus protease structure that was recently clarified by a German scientific team. With pride he notes that Life Sciences solutions from GE Healthcare were involved in this research.

In under two years the Zika virus (ZIKV) has gone from being almost unknown to being at the center of a global health emergency. So far ZIKV has affected more than 60 nations mainly in South and Central America, and it continues to spread. The epidemic of ZIKV in Brazil has been particularly concerning, because the virus is suspected to have caused many cases of microcephaly in infants, some of which resulted in death. Yet ZIKV remains poorly understood in terms of its virology, epidemiology, and consequent clinical complications.

Efforts are underway across the world to understand ZIKV, as well as to develop vaccines and therapies that can act against it and prevent its spread.

Understanding the protease structure

Scientists need a basis for developing an antiviral agent to act against ZIKV. The good news is that there has been an important breakthrough on this front. Working with his team, Prof. Rolf Hilgenfeld, Director of the Institute of Biochemistry at the University of Lübeck has taken a notable step towards developing antiviral drugs.

In a paper published in Science, the team describes how it determined the three-dimensional structure of ZIKV protease using X-rays to analyze crystals of the protein bound to an inhibitor. ZIKV requires this protease to produce replication proteins and envelope components for making new virus particles.

These results are important because, as Prof. Hilgenfeld explains, they may support the design of drugs that could be given to pregnant women prophylactically to interrupt the chain of ZIKV transmission by mosquitoes.

Getting protein of sufficient quality for crystallography

To obtain recombinant ZIKV protease for crystallization, Prof. Hilgenfeld and his team devised a protein purification method based on a standard CIPP model. (CIPP is short for Capture, Intermediate Purification, and Polishing.) Histidine-tagged protein was purified using immobilized metal affinity chromatography. After tag cleavage, the sample was purified using ion exchange chromatography, followed by polishing via size exclusion chromatography. All prepacked columns and the automated chromatography system were from GE Healthcare.

I joined GE to support our customers in solving real-life problems, so it was particularly gratifying to notice that GE Healthcare products were used in this research. Seeing our products play even a small part in the research efforts to control the ZIKV epidemic makes me and my colleagues proud. We extend our best wishes to all the scientists working on such an important global health issue.

Are you working on Zika virus? Let us know your thoughts, tips, or problems faced. Post your comment below or join in the discussion forums.