Researchers from the LSU Health New Orleans School of Medicine have identified the fragment of the Ebola virus protein that is toxic to cells and may contribute to infection and illness. The opensource study is published in the open access journal Viruses.
The fragment was found within a grouping of amino acids that is made in parallel with the protein involved in attachment of the virus to cells. Called the Delta peptide, it has been shown recently to block the Ebola virus from attaching to already-infected cells. The new findings suggest that Delta peptide possibly functions by changing membrane permeability.
The team then set out to produce a structural model and potential mechanism of action. The results of this modelling work were fashioned into a manuscript that was subjected to rigorous peer view by experts in the field.
Although preliminary studies using synthetic peptides have confirmed the potential of the fragment, its specific role and potency in its natural environment within Ebola virus-infected cells are yet to be determined. However, the team have determined how to deactivate the toxic properties of the Ebola protein fragment in the laboratory environment.
The researchers are also developing inhibitors of the toxic mechanism, which may ultimately be useful as drugs, should a role for Delta peptide in Ebola virus disease become established by future studies.
This discovery is the latest in a series of discoveries by the team. They were the first to identify and publish the entry peptide sequence of HIV-1 in 1987, and the first to model the structure of the HIV-1 entry protein in 1989. Those studies defined a superfamily of viral entry proteins subsequently named by others as ‘Class I fusion/entry glycoproteins.’
The ‘Gallaher model’ of HIV-1 also directly led to the development of the drug Fuzeon, an inhibitor of HIV-1 entry used as therapy for HIV disease. The team were also the first to identify and model the entry peptide loop and entry protein of Ebola virus in 1996.
According to the Centers for Disease Control and Prevention (CDC), the 2014 Ebola epidemic is the largest in history, affecting multiple countries in West Africa. Two imported cases, including one death, and two locally acquired cases in healthcare workers have been reported in the United States. As of January 16, 2015, the CDC and World Health Organization report 13,510 laboratory-confirmed cases and 8,483 deaths worldwide.
Source: LSU Health New Orleans School of Medicine
![Model for Ebola virus delta peptide. A model of the 40 amino acid peptide sequence of Ebola virus 2014 (EBOV/SLE14-EM95) delta peptide was rendered in PyMol [36] using secondary structural predictions from PredictProtein [40] for the amino terminal half. The carboxyl terminal half of the delta peptide is depicted as an amphipathic alpha helix to emphasize the alignment of positively charged amino acids (lysine and arginine, blue). The carboxyl terminus may not form an alpha helix in a potential alternative configuration of delta peptide in which cysteine 29 and 38 (colored gold) are disulfide-bonded. Aromatic amino acids (tyrosine and tryptophan) are colored black, serine and threonines are colored green, glutamine is colored violet, and the negatively charged amino acid glutamic acid is colored red. The adduct sugar moiety indicates the site of O-glycosylation of delta peptide at threonine 9 of the peptide; the innermost N-acetyl galactosamine is shown in salmon, galactose in purple, and the terminal N-acetyl neuraminic (sialic) acid in cyan. A potential additional O-linked glycan is present at threonine 5. Modeling of the Ebola Virus Delta Peptide Reveals a Potential Lytic Sequence Motif. Garry et al 2015.](https://i0.wp.com/health-innovations.org/wp-content/uploads/2015/01/lsu-health-new-orleans-identifies-toxic-ebola-protein-fragment-healthinnovations1.png?ssl=1)
