Computational search for drug repurposing to identify potential inhibitors against SARS-COV-2 using Molecular Docking, QTAIM and IQA methods in viral Spike protein - Human ACE2 interface

摘要

With the advancement of the Covid-19 pandemic, this work aims to find molecules that can inhibit the attraction between the Spike proteins of the SARS-COV-2 virus and human ACE2. The results of molecular docking positioned four molecules at the interaction site Tyr-491(Spike)-Glu-37(ACE2) and one at the site Gly-488(Spike)-Lys-353(ACE2). The QTAIM and IQA data showed that the 1629 molecule had a significant inhibitory effect on the Gly488-Ly353 site, decreasing the Laplacian of the electronic density of the BCP O-4-N-10. The molecule 2542 showed an inhibitory effect in two regions of interaction of the Tyr491-G1u37 site, acting on the BCPs H-30-H-33 and O-8-H (31) while the ligand 2600, in conformation 26, presented a similar effect only on the BCP O-8-H-31 of that same interactive site. Thus, the data suggest laboratory tests of a combination of molecules that can act at two sites of interaction simultaneously, using the combination of 1629/2542 and 1629/2600 ligands. (C) 2021 Elsevier B.V. All rights reserved.