Ebola treatments could be affected by virus mutations

The Ebola virus
The Ebola virus | Courtesy of the CDC

A recent study identified genetic mutations in the strain of Ebola virus behind the current outbreak in West Africa that could hinder potential sequence-based treatment options.

Results of the study were published in Mbio, the online open-access journal of the American Society for Microbiology.

The research dates back four decades and traces the genetic mutations that have taken place in the virus. The findings conclude experimental, sequence-based therapeutic treatments could possibly be affected due to changes in the composition of the strain.

"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 countermeasures," 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, said.

A number of drugs currently being developed to combat Ebola bind to and target a segment of the genetic or protein sequence of the virus. The drugs may not be as effective if the sequence changes because of genetic drift.

"Our work highlights the genetic changes that could affect these sequence-based drugs that were originally designed in the early 2000s based on virus strains from outbreaks in 1976 and 1995," Palacios said.

The study compared the complete genomic sequence of the current outbreak strain EBOV/Mak with the EBOV/Yam-May alternation from an outbreak in Yambuku, Zaire, in 1976 and the EBOV/Kik-9510621 strain from an outbreak in Kikwit, Zaire, in 1995. Research revealed single nucleotide polymorphisms in more than 600 spots, or roughly 3 percent of the genome.

Sequence-based Ebola treatments have not been approved by the U.S. Food and Drug Administration or other regulatory agencies; however, a clinical trial is scheduled to take place in Sierra Leone.

"The virus has not only changed since these (sequence-based) therapies were designed, but it's continuing to change," U.S. Army Capt. Jeffrey Kugelman, lead author and a viral geneticist at USAMRIID, said. "Ebola researchers need to assess drug efficacy in a timely manner to make sure that valuable resources are not spent developing therapies that no longer work."

Research was confined to those mutations that altered the genetic sequences. Ten new mutations were discovered that interfere with the actions of monoclonal antibody, siRNA (small-interfering RNA) or PMO (phosphorodiamidate morpholino oligomer) drugs that are currently in the testing phase.