Hunting vulnerable targets on Dengue

NUS biological scientists have discovered hidden targets on the Dengue virus during transmission into human hosts.

The Dengue virus changes its shape during transmission from the mosquito vector to the human host. An NUS team, comprising Prof Ganesh S. ANAND, Mr LIM Xin Xiang, Dr Arun CHANDRAMOHAN and collaborators Prof Thorsten WOHLAND (NUS), Prof Shee-mei LOK (Duke-NUS) and fellow research scientists has captured how certain strains of Dengue virus puff up at human body temperatures of 37 ºC (healthy) and 40 ºC (Dengue-infected). Using molecular measurements, they have uncovered important hidden targets on the surface of the Dengue virus that are more exposed when the virus changes in shape. These hidden targets represent important therapeutic target sites to counter Dengue infection.

Dengue infection is a serious global healthcare problem affecting about 400 million people worldwide. It is one of the major mosquito-borne diseases in Singapore. Currently, there are no effective therapeutics available to tackle dengue. This highlights the urgent need for a novel approach in devising strategies to block dengue infection and related classes of viral diseases including Zika. The recent findings reported by Lim et al. (2017) represent a breakthrough in uncovering new vulnerabilities in the Dengue virus as it moves from the mosquito into an unsuspecting human host.

By monitoring how the Dengue virus changes its shape at human host temperatures, their current work has identified vulnerable targets on the viral surface. These findings hold enormous potential for devising a new strategy to block Dengue infection by targeting these weak spots. These weak spots that are exposed on the virus surface only in its host offers the potential to specifically target the vulnerabilities of the Dengue virus inside the human patient’s body. This is an unprecedented and important novel strategy to counter viral epidemics in Singapore and the world.

The research group is expanding plans for applying knowledge of the molecular features of the Dengue virus to develop antibody drugs and for vaccination strategies against Dengue. The researchers are also extending these strategies to the closely related Zika virus and other viral threats to Singapore.

Figure showing the Dengue virus being transmitted to an unsuspecting human through a mosquito bite. Upon transmission into the human host, the Dengue virus puffs up in size. The team has uncovered hidden targets on the Dengue virus by capturing changes in the virus structure. Targeting these vulnerabilities represents a novel strategy to combat Dengue infections.

Reference

Lim XX; Chandramohan A; Lim XYE; Bag N; Sharma KK; Wirawan M; Wohland T; Lok SM; Anand GS*, “Conformational changes in intact dengue virus reveal serotype-specific expansion.”, NATURE COMMUNICATIONS Volume: 8, Article number: 14339 DOI: 10.1038/ncomms14339 Published: 2017.