|A new universal drug target for Ebola has been discovered.|
Biochemists have reported a new drug discovery tool against the Ebola virus. According to a study published in this week's online edition of Protein Science, they have produced a molecule, known as a peptide mimic, that displays a functionally critical region of the virus that is universally conserved in all known species of Ebola. This new tool can be used as a drug target in the discovery of anti-Ebola agents that are effective against all known strains and likely future strains.
The Utah scientists designed peptide mimics of a highly conserved region in the Ebola protein that controls entry of the virus into the human host cell, initiating infection. Importantly, the researchers were able to demonstrate this peptide target is suitable for use in high-throughput drug screens. These kinds of screens allow rapid identification of potential new drugs from billions of possible candidates. Current experimental drugs generally target only one of Ebola's five species.
Ebola is a lethal virus that causes severe hemorrhagic fever with a 50 percent to 90 percent mortality rate. There are five known species of the virus. Outbreaks have been occurring with increasing frequency in recent years, and an unprecedented and rapidly expanding Ebola outbreak is currently spreading through several countries in West Africa with devastating consequences. The development of an effective anti-Ebola agent to protect against natural outbreaks and potential bioterror exposures is an urgent global health need. There are no approved anti-Ebola agents, but a number of promising experimental drugs are being aggressively advanced to clinical trials to address the current crisis.
Of particular interest, this target was shown to be suitable for the discovery of mirror-image peptide inhibitors (D-peptides), which are promising drug candidates. Unlike natural peptides, they are not digested by enzymes in the blood. D-peptides are also much simpler and less expensive to produce compared to the current most promising approach, antibodies. The group has previously developed highly potent and broadly acting D-peptide inhibitors of HIV entry, currently in preclinical studies, and is now adapting this approach to Ebola using the mimics developed in this study.