Taking a step further in identifying a possible therapy for the Zika infection, researchers have discovered the mechanism by which a human antibody previously identified to react with the Dengue virus, prevents Zika infection at a cellular level.
Previously, the antibody C10 was identified as one of the most potent antibodies able to neutralise Zika infection. The new study, published in the journal Nature Communications, determines how C10 prevents the infection.
“By defining the structural basis for neutralization, these studies provide further support for the idea that this antibody will protect against Zika infection, potentially leading to a new therapy to treat this dreaded disease,” said Ralph Baric, Professor at University of North Carolina.
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 (potential of hydrogen, a scale of acidity), 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.
“Hopefully, these results will further accelerate the development of C10 as a Zika therapy to combat its effects of microcephaly (a birth defect) and Guillain-Barre (paralysis) syndrome,” one of the researchers Lok Shee-Mei from Duke-National University of Singapore Medical School in Singapore.