Design of short peptides targeting the interaction between SARS-CoV-2 and human ACE2

Abstract

In the end of 2019, a novel coronavirus called SARS-CoV-2 has appeared in Wuhan, China and caused a pandemic outbreak by overwhelming deadly infections around the work. By comparing to its ancestor, SARS-CoV, it is more infectious and shows much more tight binding with host cells. One of the main units of this coronavirus is spike (S) protein which has two subunits called S1 and S2. Subunit S1 contains receptor binding domain (RBD) that takes role in initiating entry into the cells by interacting with human angiotensin converting enzyme 2 (ACE2) receptor. And S2 subunit ensures the fusion between host and viral cell membranes in meantime. Different drug development researches were studied and several therapeutics developed during the pandemic time such as antibodies and vaccines. Differing from traditional drug developments methods, peptides as inhibitor are promising drug compound due to their efficiency, lesser immunogenicity, easiness of removal from body and they have higher diffusivity through tissues and organs because of their smallness. Considering these advantages of peptides, several studies have been made with knowing antiviral peptides by different research groups. In present study, what we aimed to develop novel peptides to use against spike RBD. Unlike by using known peptides from the literature, we try to use as much possible as combination of short peptides. First, we created peptides of random sequences, after that we docked them to spike RBD protein by using AutoDock CrankPep (ADCP). For deciding to use the proper docking tool, we have done a comparison work between free docking tools (Vina and ADCP) which are developed by AutoDock Software. After finishing the dockings, top ones with highest binding energy result are selected for the next step which is Molecular Dynamics (MD) simulations. Results of simulations are controlled according to their RMSD trajectory and binding energy. At the end, one sequence, "wfdwef", stood out as promising over the others. For further, this finding can be used as potential inhibitor for coronavirus after experimental studies