Genetic changes in Ebola virus in West African outbreak could hinder potential treatments

Researchers have tracked the genetic mutations that have occurred in the Ebola virus during the last four decades. Their findings, published in mBio, the online open-access journal of the American Society for Microbiology, identified changes in the current West African outbreak strain that could potentially interfere with experimental, sequence-based therapeutics.

Many 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, the drugs may not work effectively.

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.

The sequence-based drugs currently offer the best hope for future treatment of Ebola outbreaks, but they have not yet been approved by the U.S. Food and Drug Administration or any other regulatory agency. Because the World Health Organization adopted emergency containment measures for the ongoing West African outbreak, these drugs are currently being used to treat a small number of patients in experimental testing. A clinical trial for one therapy will begin in Sierra Leone in the coming months.

The team then narrowed its search to those mutations that changed the genetic sequences targeted by the various drugs. Of those, they found 10 new mutations that might interfere with the actions of monoclonal antibody, siRNA (small-interfering RNA), or PMO (phosphorodiamidate morpholino oligomer) drugs currently being tested. The authors conclude that drug developers should check whether these mutations affect the efficacy of the therapeutic drug.