Zika viruses: Developing reliable diagnostics and new active agents

At the German Center for Infection Research (DZIF), research projects can be initiated within a week via a fast track procedure if required. This is especially relevant to emerging infections and hospital pathogen outbreaks. Currently, DZIF scientists are developing new active agents against the Zika virus as well as a reliable standard diagnostic test.

The current Zika outbreak in Central and South America has shown that emerging infections like Zika still require a great deal of research. How will the virus spread in the near future, how many people have actually been affected, and which side effects are of concern? Reliable diagnostics are of major importance to both the patient and the further research on its spread. Developing rapidly effective drugs against the virus, which has already affected millions of people, is equally important. At the DZIF, both these tasks are now being taken on at high speed.

Active agents against the Zika virus

“Currently, there is neither a vaccine nor a drug available against the Zika virus,” explains DZIF scientist Rolf Hilgenfeld from the University of Lübeck. Together with his colleagues from the University of Heidelberg, Prof Rolf Bartenschlager and Prof Christian Klein, he is aiming at filling this gap as quickly as possible. The research group’s aim is to decipher three dimensional enzyme structures in the virus and to develop active agents that target these and inhibit viral replication. At the DZIF, the scientists have already developed the basis for a cell culture system in which Zika viruses can be examined. The scientists can also draw on many promising viral structures that could serve as target regions for antiviral agents.

“The responsible people in the project unite the required expertise in structural biology, flavivirus virology as well as medicinal chemistry,” emphasizes Prof Stephan Becker, coordinator of the research field “Emerging Infections”. He believes that the project will render positive results within a year.

Reliable diagnosis

The second newly funded DZIF project also requires rapid results. “Currently, mainly virus genome testing in blood and urine is being used to detect acute Zika infections,” explains Prof Felix Drexler, who is scrutinizing the existing tests together with Prof Christian and his team at the University of Bonn. Their investigations have demonstrated that the commonly used assays are often not sensitive enough to detect smaller amounts of the virus in the outbreak regions. Additionally, not all virus strains are detected uniformly across the different testing systems. “We urgently need standardised tests that can be implemented globally,” Drexler explains. “The industrial kits for detecting Zika viruses which have been brought into the market over the last months are often not affordable for the affected countries.”

The researchers from Bonn have already developed a control test which not only validates each specific test, but also quantifies viral RNA in blood and urine. The so-called “calibrator” used for this is synthetically manufactured RNA which contains the different viral RNA target regions used in the common tests. They now want to expand this control test to include molecular detection of dengue and chikungunya viruses. These viruses are currently also circulating in Latin America, cause symptoms similar to those of Zika infections and could influence the course of Zika infections. The standardised testing systems and controls are to be developed further for global use. “All our results will be contributed to activities in Brazil and to the WHO which is coordinating the fight against the Zika virus outbreak,” Drexler explains.

Further Zika research at the DZIF

The above mentioned projects only constitute a part of the Zika virus research taking place at the DZIF. Further topics include:

Prof Jonas Schmidt-Chanasit has been coordinating Zika virus research at the Bernhard Nocht Institute (BNI) in Hamburg since 2013. Here, the first specific Zika virus antibody test was developed together with the company EUROIMMUN. Besides this, there is an ongoing project which aims to elucidate the factors that influenced the emergence and course of the Zika virus epidemic. The results will be used to initiate mosquito eradication measures early on, so that they can take effect on the course of the epidemic.

In order to better assess the risk of a Zika epidemic occurring in Germany, scientists at the BNI are infecting local mosquitos with Zika viruses under laboratory conditions, to investigate whether they can transmit the virus. Laboratories have been set up for further studies in regions endemic to Zika. These studies concentrate on investigating the viral ecology as well as more closely examining the course of Zika infections during pregnancy.

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