Biomimetic Design of Peptide Neutralizer of Ebola Virus with Molecular Simulation

Ebola virus (EBOV) belongs to the Filoviridae family, which can cause severe hemorrhagic fever in humans and nonprimates. The neutralization of EBOV by monoclonal antibody (mAb) ADI-15946 was reported recently. In the present study, the molecular interactions between the receptor GPcl of EBOV and ADI-15946 were studied by molecular dynamics (MD) simulation and molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) analysis. Hydrophobic interaction was identified as the main driving force for the binding of ADI-15946 on EBOV. Moreover, the contribution of each amino acid residue for the binding was evaluated. Then, an affinity binding model (ABM) was constructed using the residues favorable for the binding, including Y107, F108, D109, W110, and R113. The biomimetic design of neutralizer against EBOV according to the ABM of ADI-15946 was then performed, followed by screening using docking, structural similarity. Two neutralizers YFDWHMR and YFDWRYR were obtained, which were proven to be capable of strong binding on GPcl and then neutralizing GPcl. These results would be helpful for the development of neutralizers for Ebola virus.