A human protein called RBBP6 helps fight the Ebola virus by interfering with its replication cycle, and a small molecule drug that mimics the function of this protein could one day be an effective therapy against the deadly disease, according to a study recently published in Cell.
“One of the scariest parts about the 2014 Ebola outbreak was that we had no treatments on hand; tens of thousands of people became sick and thousands of people died because we lacked a suitable treatment,” said Judd Hultquist, PhD, assistant professor of Medicine in the Division of Infectious Diseases and the co-lead author of the study. “Part of the goal of this work was to better understand the biology behind Ebola viruses, so that we could better develop next-generation therapeutics.”
Ebola virus, like other viruses, invades host cells and uses them to replicate, usurping cellular processes to build viral proteins, which eventually become new copies of the virus. In the current study, Hultquist and his collaborators used mass spectrometry to search for interactions between human proteins and Ebola proteins, finding strong evidence for an interaction between Ebola protein VP30 and the human protein RBBP6.
Further structural and computational analysis narrowed the interaction down to a small, 23-amino acid-long peptide chain. This small group of amino acids alone is sufficient to disrupt the Ebola virus life cycle, Hultquist said.
“If you take that peptide and put it into human cells, you can block Ebola virus infection,” Hultquist said. “Conversely, when you remove the RBBP6 protein from human cells, Ebola virus replicates much faster.”
Proteins like RBBP6 that can block the replication of viruses are called “restriction factors.” As a virus evolves proteins to bypass the body’s defenses, human cells in turn develop defense mechanisms against those viruses — an evolutionary arms race that could last for millions of years. According to Hultquist, this particular defense mechanism has therapeutic potential.
“What we envision is a small molecule drug that mimics the peptide, and could be used in response to an Ebola virus outbreak,” Hultquist said.
Emerging diseases will impact new areas as the world continues to become more interconnected and globalized, Hultquist said. In addition, the looming specter of climate change promises to broaden the reach of vector-borne diseases — by expanding the range of mosquitos, for example — requiring new strategies in curbing disease outbreaks.
Until recently, many diseases in the developing world, including Ebola virus, have been comparatively understudied, according to Hultquist.
“It wasn’t until the outbreak of 2014 that other countries started seriously worrying about the potential for a larger epidemic,” Hultquist said. “It’s no longer going to be a local problem that people can afford to ignore. We should be taking a much more proactive stance against some of these neglected viruses and be studying them in real time — so the next time an outbreak does occur, we’re ready for it.”
This work was supported by National Institutes of Health grants P50GM082250, U19AI106754, R01AI120694, P01AI063302, U19AI109664, U19AI109945, P01120943 and R01AI114814.