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...

Description complète

Enregistré dans:
Détails bibliographiques
Auteurs principaux: 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
Format: article
Langue:EN
Publié: American Society for Microbiology 2015
Sujets:
Accès en ligne:https://doaj.org/article/5ef0d8f2b05d47a7be7da09ed079334e
Tags: Ajouter un tag
Pas de tags, Soyez le premier à ajouter un tag!
Description
Résumé: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.