Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics
Jeffrey R. Kugelman,
Mariano Sanchez-Lockhart,
Kristian G. Andersen,
Stephen Gire,
Daniel J. Park,
Rachel Sealfon,
Aaron E. Lin,
Shirlee Wohl,
Pardis C. Sabeti,
Jens H. Kuhn,
Gustavo F. Palacios
Affiliations
Jeffrey R. Kugelman
Center for Genome Sciences Division of the United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA
Mariano Sanchez-Lockhart
Center for Genome Sciences Division of the United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA
Kristian G. Andersen
Center for Systems Biology, Harvard University, Cambridge, Massachusetts, USA
Stephen Gire
Center for Systems Biology, Harvard University, Cambridge, Massachusetts, USA
Daniel J. Park
Center for Systems Biology, Harvard University, Cambridge, Massachusetts, USA
Rachel Sealfon
Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
Aaron E. Lin
Center for Systems Biology, Harvard University, Cambridge, Massachusetts, USA
Shirlee Wohl
Center for Systems Biology, Harvard University, Cambridge, Massachusetts, USA
Pardis C. Sabeti
Center for Systems Biology, Harvard University, Cambridge, Massachusetts, USA
Jens H. Kuhn
Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA
Gustavo F. Palacios
Center for Genome Sciences Division of the United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA
ABSTRACT Until recently, Ebola virus (EBOV) was a rarely encountered human pathogen that caused disease among small populations with extraordinarily high lethality. At the end of 2013, EBOV initiated an unprecedented disease outbreak in West Africa that is still ongoing and has already caused thousands of deaths. Recent studies revealed the genomic changes this particular EBOV variant undergoes over time during human-to-human transmission. Here we highlight the genomic changes that might negatively impact the efficacy of currently available EBOV sequence-based candidate therapeutics, such as small interfering RNAs (siRNAs), phosphorodiamidate morpholino oligomers (PMOs), and antibodies. Ten of the observed mutations modify the sequence of the binding sites of monoclonal antibody (MAb) 13F6, MAb 1H3, MAb 6D8, MAb 13C6, and siRNA EK-1, VP24, and VP35 targets and might influence the binding efficacy of the sequence-based therapeutics, suggesting that their efficacy should be reevaluated against the currently circulating strain.
