title: Evaluation of the potential impact of Ebola virus genomic drift on the efficacy of sequence-based candidate therapeutics.
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.
authors.affiliation: Center for Genome Sciences Division of the United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA.
authors.forename: Jeffrey R
authors.identifier: http://orcid.org/0000-0001-7442-9684
authors.initials: JR
authors.lastname: Kugelman
authors.affiliation: Center for Genome Sciences Division of the United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA.
authors.forename: Mariano
authors.initials: M
authors.lastname: Sanchez-Lockhart
authors.affiliation: Center for Systems Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Kristian G
authors.initials: KG
authors.lastname: Andersen
authors.affiliation: Center for Systems Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Gire
authors.affiliation: Center for Systems Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Park
authors.affiliation: Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Sealfon
authors.affiliation: Center for Systems Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Aaron E
authors.initials: AE
authors.lastname: Lin
authors.affiliation: Center for Systems Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Shirlee
authors.initials: S
authors.lastname: Wohl
authors.affiliation: Center for Systems Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Pardis C
authors.initials: PC
authors.lastname: Sabeti
authors.affiliation: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA.
authors.forename: Jens H
authors.identifier: http://orcid.org/0000-0002-7800-6045
authors.initials: JH
authors.lastname: Kuhn
authors.affiliation: Center for Genome Sciences Division of the United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA gustavo.f.palacios.ctr@us.army.mil.
authors.forename: Gustavo F
authors.initials: GF
authors.lastname: Palacios
mesh_terms: D029043:Ebolavirus / Q000235:genetics*; D014644:Genetic Variation; D023281:Genomics; D019142:Hemorrhagic Fever, Ebola / Q000628:therapy / Q000821:virology*; D006801:Humans; D009154:Mutation; D034741:RNA, Small Interfering; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D014764:Viral Proteins