Molecular Docking and Dynamics Simulation of a Screening Library from Life Chemicals Database for Potential Protein-Protein Interactions (PPIs) Inhibitors against SARS-CoV-2 Spike Protein

Abstract

The ongoing pandemic of coronavirus 2 represents a major challenge for global public health authorities. Coronavirus disease 2019 can be fatal especially in elderly people and those with comorbidities. Currently, several vaccines against coronavirus 2 are under application in multiple countries with emergency use authorization. In the same time, many vaccine candidates are under development and assessment. It is worth noting that the design of some of these vaccines depends on the expression of receptor binding domain for viral spike protein to induce host immunity. As such, blocking the spike protein interface with antibodies, peptides or small molecular compounds can impede the ability of coronavirus 2 to invade host cells by intervention with interactions between viral spike protein and cellular angiotensin converting enzyme 2. In this virtual screening study, we have used predictive webservers, molecular docking and dynamics simulation to evaluate the ability of 3000 compounds to interact with interface residues of spike protein receptor binding domain. This library of chemicals was focused by Life Chemicals as potential protein-protein interactions inhibitor. Here, we report that hit compound 7, with IUPAC name of 3‐cyclohexyl‐N‐(4‐{[(1R,9R) ‐6‐oxo‐7,11‐ diazatricyclo [7.3.1.02,7] trideca‐2,4‐dien‐11‐yl] sulfonyl} phenyl) propenamide, may have the capacity to interact with interface of receptor binding domain for viral spike protein and thereby reduce cellular entry of the virus. However, in vitro and in vivo assessments may be required to validate these virtual findings.