Abstract
The 2014 outbreak of Ebola virus disease (EVD) in Western Africa is the largest recorded filovirus disease outbreak and led to the death of over 11,000 people. The recent EVD outbreaks (since May 2018) in the Democratic Republic of the Congo has already claimed the lives of over 250 people. Tackling Ebola virus (EBOV) outbreaks remains a challenge. Over the years, significant efforts have been put into developing vaccines or antibody therapies which rely on an envelope glycoprotein (GP) of Zaire ebolavirus (strain Mayinga-76). Therefore, one key approach for combating EVD epidemics is to predict mutations that may diminish the effectiveness of the treatment. In a previous study we generated a watch list of potential antibody escape mutations of EBOV GP against the monoclonal antibody KZ52. Molecular modeling methods were applied to the three-dimensional experimental structure of EBOV GP bound to KZ52 to predict the effect of every possible single mutation in EBOV GP. The final watch list contained 34 mutations that were predicted to destabilize binding of KZ52 to EBOV GP but did not affect EBOV GP folding and its ability to form trimers. In this study, we expand our watch list by including three more monoclonal antibodies with distinct epitopes on GP, namely Antibody 100 (Ab100), Antibody 114 (Ab114) and 13F6-1-2. Our updated watch list contains 127 mutations, three of which have been seen in humans or are experimentally associated with reduced efficacy of antibody treatment. We believe mutations on this watch list require attention since they provide information about circumstances in which interventions could lose the effectiveness.
Highlights
Ebolavirus has six known species: Zaire ebolavirus, Sudan ebolavirus, Taï Forest ebolavirus, Bundibugyo ebolavirus, Reston ebolavirus and Bombali ebolavirus. [1, 2] Ebola virus (EBOV) is deadly and can led to death in up to 90% cases
We focused on the KZ52 monoclonal antibodies (mAbs) as it had a 3-D experimental structure bound to EBOV GP available
Structures of Antibody 100 (Ab100) and Antibody 114 (Ab114) bound to EBOV GP were obtained from the Protein Data Bank (PDB) accession number 5FHC.[18]
Summary
Ebolavirus has six known species: Zaire ebolavirus, Sudan ebolavirus, Taï Forest ebolavirus, Bundibugyo ebolavirus, Reston ebolavirus and Bombali ebolavirus. [1, 2] Ebola virus (EBOV) is deadly and can led to death in up to 90% cases. Ebolavirus has six known species: Zaire ebolavirus, Sudan ebolavirus, Taï Forest ebolavirus, Bundibugyo ebolavirus, Reston ebolavirus and Bombali ebolavirus. [1, 2] Ebola virus (EBOV) is deadly and can led to death in up to 90% cases. The Ebola virus disease (EVD) outbreak in Western Africa between 2014 to 2016 is the largest recorded filovirus disease outbreak and led to death over 11,000 people.[3] This outbreak receded in 2016, but there are two recent EVD outbreak in the Democratic Republic of the Congo that began in May and August 2018 which. Expanded watch list and Ebola virus antibody escape mutations. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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