April 2019 | Issue 41
Delving deeper into the world of molecular virology

Amanda LEE (use this).pngBy Amanda Lee, Senior Assistant Manager (Media), Communications and Outreach

When Severe Acute Respiratory Syndrome (SARS) first struck Singapore back in 2003, LKCMedicine
Nanyang Assistant Professor Luo Dahai was just into his second year of undergraduate studies in Biological Sciences at Nanyang Technological University, Singapore (NTU).

He vividly remembers the outbreak trail across the world then as SARS left more than 700 dead in 37 countries. Singapore, alone, recorded 33 deaths.

“That outbreak was one of the striking things that happened all around the world in 2003. I didn’t know that a virus can be so devastating, so I became interested to know more about them,” said Asst Prof Luo.

Fifteen years on, Asst Prof Luo is now an accomplished scientist who studies the molecular mechanisms of viral infection and host defence. He joined LKCMedicine in 2013.

His love for science began in primary school in his hometown, Shandong, China. He later moved to Singapore after receiving a scholarship from the Ministry of Education in 2001. The following year, Asst Prof Luo began his undergraduate studies at the School of Biological Sciences in NTU.

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LKCMedicine Nanyang Assistant Professor Luo Dahai said he is driven by curiosity to think deeper about many things

“It is interesting to know about nature and most of the time, I’m driven by curiosity to think deeper about many things,” he added. His curiosity has certainly paved his career in the science field where he has carved a name for himself. Last year, Asst Prof Luo received the Nanyang Research Award (Young Investigator), which is given to individuals for their contributions toward knowledge frontiers.

In 2017, he received the prestigious EMBO Young Investigator Award, making him one of only four EMBO Young Investigators from Asia and the first in NTU to clinch the award. Asst Prof Luo was given the award for his contributions to RNA viruses and host defence, in particular, his breakthrough about the structure of NS2B-NS3 – two key virus replication proteins – found in common flaviviruses such as dengue, Zika
and West Nile.

In 2013, he began his project on the NS2BNS3 protease. However, he looked deeper into the project in 2016 when the Zika virus swept across the globe – including Singapore. In August that year, the Singapore health ministry announced the first case of local Zika virus transmission. The consequences of flaviviruses can be unforgiving, as it causes several human diseases – such as yellow fever, dengue fever, hepatitis C and even various types of encephalitis.

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, Asst Prof Luo found that the established design of using artificial linkers to study these proteins reduce the accuracy of the data gathered, hampering the drug discovery process. By successfully combining NS2B and NS3 without a linker, the team recorded what is likely the proteins’ native state. This helped to shed light on the proteins’ exact function,
structure and suitability for structure-based drug development.

"Some of these proteins are responsible for replication, so that's the area at the moment that our lab is interested in. Within this complex, the N2B-NS3 protease is one essential component and it's responsible to process the polyprotein to make them mature and functional," explained Asst Prof Luo.

"Obviously if the protease is essential in replication, it can be considered as a target to develop an antiviral drug. This is why we are interested in this viral target as we want to better understand it and hopefully develop an inhibitor and kill the virus," he added.

The NS2B-NS3 protease project is one of the major projects that Asst Prof Luo's team is currently working on. His team is also researching on chikungunya virus. "Here, we are focused on the virus replication process, how it is propagated. At the same time, we try to step out of our comfort zone so we pick up the chikungunya virus. That's less well-known than dengue or Zika, but with outbreaks from time to time".

"In the literature, there's very little known about the chikungunya virus; we consider that as an opportunity because less is known," he said.

As an expert in the molecular biology of viruses, Asst Prof Luo shared that flaviviruses such as Zika and dengue are easily spread due to human density. While the most effective way to eliminate the viruses is by killing the mosquitoes, it is not realistic and with unpredictable consequence to eliminate a species from the planet, he added.

"It may be effective to control the mosquitoes in Singapore because we are a city-state, as compared to other countries. However, in the long run, whether it's for Singapore or the world, you still need a vaccine or antivirus against these diseases," said Asst Prof Luo. That's the mission that Asst Prof Luo has set his sights on.