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.
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