Scientists say they’ve figured out how a human antibody called C10 prevents Zika infection at a cellular level.
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.
“Hopefully, these results will further accelerate the development of C10 as a Zika therapy to combat its effects of microcephaly and Guillain-Barré syndrome.”
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 visualizes extremely small particles and their interactions, the team could visualize 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 can’t enter and infect the cell.
“Hopefully, these results will further accelerate the development of C10 as a Zika therapy to combat its effects of microcephaly and Guillain-Barré syndrome. This should emphasize the need for further studies of the effect of C10 on Zika infection in animal models,” says Lok Shee-Mei, an associate professor at Duke-NUS Medical School.
“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,” says Ralph Baric, a professor in epidemiology at UNC’s Gillings School of Global Public Health.
The study appears in Nature Communications. A grant from the Singapore Ministry of Education and the Ministry of Health, the National Research Foundation Investigatorship Award, and funding from the US National Institutes of Health supported the work.
Source: National University of Singapore