Genomic Drift in Ebola Could Interfere with Sequence-Based Drug Development

Researchers have tracked the genetic mutations that have occurred in the Ebola virus during the last four decades. Their findings, published on January 20, 2015 in mBio®, the online open-access journal of the American Society for Microbiology (ASM), identified changes in the current West African outbreak strain that could potentially interfere with experimental, sequence-based therapeutics. "We wanted to highlight an area where genomic drift, the natural process of evolution on this RNA virus genome, could affect the development of therapeutic counte-rmeasures," says Dr. Gustavo Palacios, senior author of the study and director of the Center for Genome Sciences at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) in Frederick, Maryland. Many of the most promising drugs being developed to fight Ebola are therapeutics that bind to and target a piece of the virus's genetic sequence or a protein sequence derived from that genetic sequence. If that sequence changes due to genetic drift, the natural evolution of the virus over time, then the drugs may not work effectively. "Our work highlights the genetic changes that could affect these sequence-based drugs that were originally designed in the early 2000's based on virus strains from outbreaks in 1976 and 1995," says Dr. Palacios. The research team compared the entire genomic sequence of the current outbreak strain, called EBOV/Mak, with two other Ebola virus variants--one from an outbreak in Yambuku, Zaire (now the Democratic Republic of the Congo) in 1976 called EBOV/Yam-May, and one from an outbreak in Kikwit, Zaire in 1995 called EBOV/Kik-9510621. They found changes, called single nucleotide polymorphisms, or SNPs, in more than 600 spots, or about 3% of the genome.
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