Singapore: In a step towards developing a therapy against Zika virus, researchers have discovered the mechanism by which a human antibody previously identified to react with the Dengue virus, prevents the infection at a cellular level. As Zika spreads throughout the world, the call for rapid development of therapeutics to treat Zika rings loud and clear, researchers at Duke-NUS Medical School (Duke-NUS) in Previously, C10 was identified as one of the most potent antibodies able to neutralise Zika infection. Now, Lok Shee-Mei and her team at the Emerging Infectious Disease Programme of Duke-NUS have taken it one step further by determining how C10 is able to prevent Zika infection. To infect a cell, virus particles usually undergo two main steps, docking and fusion, which are also common targets for disruption when developing viral therapeutics.
During docking, the virus particle identifies specific sites on the cell and binds to them. With Zika infection, docking then initiates the cell to take the virus in via an endosome – a separate compartment within the cell body. Proteins within the virus coat undergo structural changes to fuse with the membrane of the endosome, thereby releasing the virus genome into the cell and completing the fusion step of infection. Using a method called cryoelectron microscopy, which allows for the visualisation of extremely small particles and their interactions, the team visualised C10 interacting with the Zika virus under different pHs, so as to mimic the different environments both the antibody and virus will find themselves in throughout infection. They showed that C10 binds to the main protein that makes up the Zika virus coat, regardless of pH and locks these proteins into place, preventing the structural changes required for the fusion step of infection. Without fusion of the virus to the endosome, viral DNA is prevented from entering the cell and infection is thwarted