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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5ef0d8f2b05d47a7be7da09ed079334e
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spelling	oai:doaj.org-article:5ef0d8f2b05d47a7be7da09ed079334e2021-11-15T15:41:19ZEvaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics10.1128/mBio.02227-142150-7511https://doaj.org/article/5ef0d8f2b05d47a7be7da09ed079334e2015-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02227-14https://doaj.org/toc/2150-7511ABSTRACT 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.Jeffrey R. KugelmanMariano Sanchez-LockhartKristian G. AndersenStephen GireDaniel J. ParkRachel SealfonAaron E. LinShirlee WohlPardis C. SabetiJens H. KuhnGustavo F. PalaciosAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 1 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 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
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.
format	article
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
title	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_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_sort	evaluation of the potential impact of ebola virus genomic drift on the efficacy of sequence-based candidate therapeutics
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/5ef0d8f2b05d47a7be7da09ed079334e
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Evaluation of the Potential Impact of Ebola Virus Genomic Drift on the Efficacy of Sequence-Based Candidate Therapeutics

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