(盐湖城)—University of Utah biochemists have reported a new drug discovery tool against the 埃博拉病毒 virus. According to a study published in this week's online edition of 蛋白质科学, 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 埃博拉病毒. This new tool can be used as a drug target in the discovery of anti-埃博拉病毒 agents that are effective against all known strains and likely future strains.
The University of Utah (U of U) work, which was funded by the National Institutes of Health, was conducted by a large collaborative team led by Debra Eckert, Ph.D., research assistant professor of biochemistry, and 迈克尔年代. 凯,M.D., Ph.D., professor of biochemistry. Key contributions to this work were provided by Dr. John Dye's laboratory at theU.S. Army Medical 研究 Institute of Infectious Diseases (USAMRIID), the lab of 克里斯托弗·P. 希尔维.菲尔。., professor and co-chair of the U of U Department of Biochemistry, and a group led by Brett Welch, Ph.D. 在Navigen， Inc., a Salt Lake City pharmaceutical discovery and development company. (Navigen has licensed exclusive rights to the technology from the U of U and is currently screening for drugs against the target.)
The Utah scientists designed peptide mimics of a highly conserved region in the 埃博拉病毒 protein that controls entry of the virus into the human host cell, initiating infection. 重要的是, 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 埃博拉病毒's five species. "The current growing epidemic demonstrates the need for effective broad-range 埃博拉病毒 virus therapies,博士说。. 特蕾西·R. Clinton, lead author on the study. “重要的是, viral sequence information from the epidemic reveals rapid changes in the viral genome, while our target sequence remains the same. 因此, our target will enable the discovery of drugs with the potential to treat any future epidemic, even if new 埃博拉病毒 virus strains emerge."
埃博拉病毒 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 埃博拉病毒 outbreak is currently spreading through several countries in West Africa with devastating consequences. The development of an effective anti-埃博拉病毒 agent to protect against natural outbreaks and potential bioterror exposures is an urgent global health need. There are no approved anti-埃博拉病毒 agents, but a number of promising experimental drugs are being aggressively advanced to clinical trials to address the current crisis.
Dr. 埃克特指出, "Although the current push of clinical trials will hopefully lead to an effective treatment for the Zaire species causing the present epidemic, the same treatments are unlikely to be effective against future outbreaks of a different or new 埃博拉病毒 species. Development of a broadly acting therapy is an important long-term goal that would allow cost-effective stockpiling of a universal 埃博拉病毒 treatment."
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, 抗体. The Utah 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 埃博拉病毒 using the mimics developed in this study. In collaboration with Navigen, several promising lead D-peptide inhibitors have already been identified. U of U and Navigen are now seeking additional funding to optimize these inhibitors and advance them into clinical trials in humans.