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 thous...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2015-02-01
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| Series: | mBio |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.02227-14 |
| _version_ | 1818990143953960960 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Jeffrey R. Kugelman |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T19:49:42Z |
| format | Article |
| id | doaj.art-5ef0d8f2b05d47a7be7da09ed079334e |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-20T19:49:42Z |
| publishDate | 2015-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-5ef0d8f2b05d47a7be7da09ed079334e2022-12-21T19:28:20ZengAmerican Society for MicrobiologymBio2150-75112015-02-016110.1128/mBio.02227-14Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate TherapeuticsJeffrey R. Kugelman0Mariano Sanchez-Lockhart1Kristian G. Andersen2Stephen Gire3Daniel J. Park4Rachel Sealfon5Aaron E. Lin6Shirlee Wohl7Pardis C. Sabeti8Jens H. Kuhn9Gustavo F. Palacios10Center for Genome Sciences Division of the United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USACenter for Genome Sciences Division of the United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USACenter for Systems Biology, Harvard University, Cambridge, Massachusetts, USACenter for Systems Biology, Harvard University, Cambridge, Massachusetts, USACenter for Systems Biology, Harvard University, Cambridge, Massachusetts, USAComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USACenter for Systems Biology, Harvard University, Cambridge, Massachusetts, USACenter for Systems Biology, Harvard University, Cambridge, Massachusetts, USACenter for Systems Biology, Harvard University, Cambridge, Massachusetts, USAIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USACenter for Genome Sciences Division of the United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/mBio.02227-14 |
| spellingShingle | 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 Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics mBio |
| title | Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics |
| title_full | Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics |
| title_fullStr | Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics |
| title_full_unstemmed | Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics |
| title_short | Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics |
| title_sort | evaluation of the potential impact of ebola virus genomic drift on the efficacy of sequence based candidate therapeutics |
| url | https://journals.asm.org/doi/10.1128/mBio.02227-14 |
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