Genetic changes in Ebola virus may hinder potential treatments

Researchers have identified genetic changes in the current strain of deadly Ebola virus behind the outbreak in West Africa which could interfere with experimental drugs.
Researchers tracked the genetic mutations that have occurred in the Ebola virus during the last four decades and identified changes in the current West African outbreak strain that could potentially interfere with experimental, sequence-based therapeutics.
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," said Gustavo Palacios, senior author of the study and director of the Center for Genome Sciences at the US Army Medical Research Institute of Infectious Diseases (USAMRIID) in Frederick, Maryland.
The 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 per cent of the genome.

The team, which included researchers from USAMRIID, Harvard University and the Massachusetts Institute of Technology, narrowed their search to only 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 concluded in the study published in mBio, the journal of the American Society for Microbiology that drug developers should check whether these mutations affect the efficacy of the therapeutic drug.

"The virus has not only changed since these therapies were designed, but it's continuing to change," said US Army Captain Jeffrey Kugelman, lead author and a viral geneticist at USAMRIID.
Three of the mutations the team found appeared during the ongoing West African epidemic which has infected a total of 21,296 people and killed 8,429 of them.
The vast majority of the deaths occurred in Guinea, Liberia and Sierra Leone.