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Ebola virus mutations may hinder new treatments
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Researchers have identified a genomic drift in the Ebola virus that may interfere with experimental treatments that were designed based on genetic sequences derived from earlier outbreaks, recent data in mBio suggest.
“The virus has not only changed since these therapies were designed, but it’s continuing to change,” study researcher Capt. Jeffrey R. Kugelman, PhD, a viral geneticist at the US Army Medical Research Institute of Infectious Diseases (USAMRIID), said in a press release. “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.”
According to Gustavo F. Palacios, PhD, director of the Center for Genome Sciences at USAMRIID, there are three types of sequence-based investigational therapies for postexposure treatment of Ebola made available to limited populations under WHO’s emergency containment protocol. These include monoclonal antibodies, small-interfering RNAs and phosphorodiamidate morpholino oligomers. None has been approved by the FDA.
Kugelman, Palacios and colleagues compared the genomic sequence of the current strain responsible for the ongoing Ebola outbreak in West Africa — named EBOV/Mak — against two previous strains that caused separate outbreaks in 1976 and 1995 in Zaire, now the Democratic Republic of Congo (EBOV/Yam-May and EBOV/Kik-9510621, respectively). When EBOV/Mak was compared against EBOV/Yam-May, the researchers identified 603 single-nucleotide polymorphisms (SNPs), representing 3.18% of the genome. When the current strain was compared against EBOV/Kik-9510621, there were 640 SNPs, making up 3.38% of the genome.
According to the researchers, 10 of the observed mutations could potentially interfere with therapies based on the Ebola genomic sequence.
“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,” Palacios said in the release. “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.”
Disclosure: The researchers report no relevant financial disclosures.
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