Ion Selective Pentameric Pore Formation by Ebola Virus Delta Peptide

Abstract

The Ebola produces the pore forming glycoprotein delta peptide which is implicated in facilitating the release of viral particles through the host cell's membrane. In this work, we investigate the molecular details of the pore forming mechanism of the delta peptide viroporin. Using information from experimental studies, we computationally modelled membrane pores formed by delta peptide oligomers. We performed all-atom molecular dynamics (MD) simulations in an explicit membrane environment to investigate the pore-forming mechanism and stability of the pores. Our results suggest that the delta peptide forms stable pentameric pores that are selective for chloride ion transport. We found that a disulfide bond between cysteine residues in the C-terminal of the peptide is essential for the pore stabilization and ion permeation. Our study provides helpful information on the pore-forming mechanism of filovirus delta peptides and such structural information can be important in designing and developing molecular modulators that target the delta peptide pore and disrupt the pathology of the Ebola virus.