December 2017 | Issue 33
Work eliminating roadblock to effective dengue, Zika drug discovery wins LKCMedicine scientist prestigious EMBO award

On 25 October this year, LKCMedicine notched another first when Nanyang Assistant Professor Luo Dahai received the prestigious EMBO Young Investigator Award. He is among 28 researchers under the age of 40 from 11 countries who were recognised by Europe's foremost life sciences body for their exceptional research and scientific potential.

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Asst Prof Luo Dahai is one of four recipients of the EMBO Young Investigator Award this year and the first from NTU

Asst Prof Luo was recognised for his contributions to RNA viruses and host defence, in particular his recent breakthrough about the structure of NS2B-NS3, two key virus replication proteins, found in common flaviviruses such as dengue, Zika and West Nile.

Leading a team of researchers from LKCMedicine, NTU’s School of Biological Sciences, NTU Institute for Structural Biology and A*Star’s Experimental Therapeutics Centre (ETC), Asst Prof Luo found that the established practice of using artificial linkers, or chemical bonds, to study these proteins actually reduces the accuracy of the data gathered, hampering the drug discovery process.

By successfully combining NS2B with NS3 without a linker, the team was able to precisely record the proteins’ native state, shedding light on their exact function, structure and suitability for structure-based drug development by identifying unique target regions that potential drugs could target to stop the replication process.

 
 

 Asst Prof Luo and his team talk about their discovery

Because the NS2B-NS3 proteins are shared by other viruses in the same family, these new insights can also be applied to the study of other disease-causing flaviviruses, such as dengue, Japanese encephalitis, and yellow fever viruses to improve the way antiviral development research is conducted.

“Through this method, we found that the information obtained about the protein structure was more accurate, and the tests based on our structure was more sensitive in picking out the lead chemical agents for further optimisation,” said Asst Prof Luo.

“Work towards finding an effective antiviral drug for the Zika virus is ongoing. We are also applying new knowledge and insights gained from this study to other similar viruses such as dengue, West Nile and Japanese encephalitis.”

To further drug discovery efforts, the research team have proceeded to additional proof-of-concept studies for a structure-based antiviral design that targets proteins needed for the Zika and dengue virus to reproduce. They are also working with scientists from ETC to develop potential drugs that can disrupt the protein and stop the virus from replicating.

Asst Prof Luo is one of four EMBO Young Investigators from Asia and the first at NTU to receive the award. He joins a network of 47 current and 417 past Young Investigators who represent some of the best up-and-coming group leaders in the life sciences in Europe and beyond.

EMBO Director Maria Leptin said, “It is a pleasure to welcome these outstanding scientists to the EMBO community. Between them, they carry out some of the most promising life science research that Europe has to offer, and we look forward to supporting them in their professional and scientific undertakings.”

During their three-year tenure, EMBO Young Investigators receive a range of benefits, including an award of 15,000 euros and possible additional funds to support the establishment of their first independent laboratories. The scientists also receive access to core facilities at the European Molecular Biology Laboratory in Heidelberg, Germany, and funding for themselves and their group members to attend conferences.

On his award, 34-year-old Asst Prof Luo said, “I am thrilled to hear the news from EMBO. It is not only recognition of the work I and my research team has done, but also the favourable environment here at NTU. It is an encouragement to continue with good science.”

Long-standing EMBO Member and LKCMedicine Professor of Developmental Biology Philip Ingham FRS said in a congratulatory message to Asst Prof Luo, “I am especially pleased to hear that you have been admitted to the Young Investigator Programme – this is great news for you and great news for LKCMedicine!”