To support the research, National Science Foundation has awarded a $66,500 (€62,00) grant to Amy Jacobs, an associate professor of microbiology and immunology at the University of Buffalo, New York.
Jacobs’ work focuses on how the Ebola virus enters cells in the human body. She believes this mechanism could be used against itself to help deliver small molecule drugs to infected cells.
“Entry research is especially fun because you can do a lot without it being dangerous. It’s exciting to think about those entry methods as potential drug delivery mechanisms as well, since you can put anything inside,” said the professor.
“We have knocked down versions of the virus that don’t have the genetic information to make it active. This allows us to safely study the outer part of the virus and its method of entry.”
Jacobs says scientists still have a lot to learn about the virus’s structure.:
“There hasn’t been a lot of research on Ebola. After this outbreak, the governmental agencies decided they should start putting some time into Ebola. We really didn’t know very much about how it gets into the cell, and we didn’t know much about the surface proteins and receptors.”
The research will also help understand other “enveloped” viruses like influenza, HIV, dengue fever and Middle East respiratory syndrome.
“All the enveloped virus research is very similar. I can easily adapt my assays by switching cells to study the entry mechanism of any of them,” she said.
The project will use atomic-level computer modelling to predict and characterise how small molecule compound probes bind to viral proteins on the surface of the Ebola virus. Jacobs will work with a team of computer scientists led by Robert Rizzo at Stony Brook University, to find these “hits” and gather small sets of molecules to be synthesized in Jacobs’ Buffalo lab.
The Stony Brook team will use a novel computational docking method that allows putative binding interfaces, such as those on Ebola viral entry proteins GP2 and GP1, to be mapped at the atomic level. They plan to identify targets in Ebola pre-hairpin and pre-fusion models using per-residue interaction energies in their computational footprinting.
The goal is to identify compounds that target the best positions for disrupting N-helical coil formation and C-helix association, using large-scale high-throughput-virtual screening of commercially available compounds and experimental testing.
“An experimental pseudotyped virus system that uses a quantitative reporter gene in a non-replicating virus-like particle containing Ebola virus envelope proteins GP2 and GP1 will be used to confirm that compounds from the virtual screen arrest viral entry/fusion. Such compounds will be prioritized for additional study and development,” said the organisation.
Jacobs’ Buffalo team is encouraging women and ethnic minorities to apply to participate in the research.