New hope in HFMD fight

Researchers from NUS and Agency for Science, Technology and Research (A*STAR) have completed the most comprehensive mapping of the susceptibility and resistance genes in the human genome that are essential for the replication processes of the Enterovirus 71 (EV71), one of the main virus serotypes that causes Hand, Foot and Mouth Disease (HFMD), paving the way for a viable treatment for the infectious disease which affects mainly young children. The research paper was published in Nature Communications in October 2016.

Singapore sees annual outbreaks of HFMD, which spikes every two to three years. More than 41,000 cases were reported in 2016. The HFMD virus strains which are prevalent in Singapore include human enteroviruses (EV71) and Coxsackieviruses (CVA6, 16), and to a lesser extent, Echoviruses.

Globally, the World Health Organization estimates that 2.8 billion people are at risk of the disease. Young children below the age of five are particularly vulnerable to the virus, and may suffer from rashes on palms and soles, as well as mouth ulcers. Occasionally in severe cases, children may suffer from complications involving the nervous and respiratory systems and heart.

There is currently no specific treatment for HFMD apart from medications to relieve the pain and fever symptoms.

Led by Associate Professor Justin Chu from NUS Yong Loo Lin School of Medicine, which is also part of the National University Health System, the team consisted of Dr Wu Kan Xing, who recently completed his PhD at NUS Medicine, as well as researchers from A*STAR. The research team employed a technology known as gene silencing, where individual genes in the entire human genome — numbering some 22,000 genes — are prevented from carrying out their respective functions.

“Once we knock down a gene, we see how the virus replication is affected,” said Assoc Prof Chu. The technique allowed the team to identify 256 human genes that are required for EV71 virus replication in human cells.

Assoc Prof Chu led the research team which completed the most comprehensive mapping of the susceptibility and resistance genes in the human genome essential for the replication processes of EV71

This was among the first of such extensive study of the human enterovirus. The study was conducted over five years and was completed in 2016.

By identifying the genes which are required for virus replication, Assoc Prof Chu said that they could better comprehend the mechanism of the virus. “By understanding how the virus infects cells and the mechanism, we can now design specific drug targets,” he explained. He hopes that repurposing existing approved drugs to target pathways which assist in virus replication would accelerate the process of developing next-generation drugs to reduce HFMD in the Singapore setting.

Assoc Prof Chu’s laboratory is concurrently working to develop a multivalent vaccine that could stop HFMD and be suitable for the Singapore population. The vaccine will target the human enteroviruses that are prevalent and causing HFMD in Singapore.

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