Details

Autor(en) / Beteiligte

• Faria, Sergio H.D.M.
• Teleschi, João G.

Titel

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

Ist Teil von

• Journal of molecular structure, 2021-05, Vol.1232, p.130076-130076, Article 130076

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• •Molecular docking and quantum chemistry methods were used to identify potential inhibitors against SARS-COV-2.•Of the five drugs studied, three showed the potential to inhibit the interaction between viral Spike and ACE2-human proteins.•The combination of two drugs, 1629/2542, would have a greater inhibitory potential because the effect would occur at two binding sites simultaneously.•The presence of all ligands created large changes in electrical charges in the atoms responsible for the interactions between the proteins Spike and ACE2.•The use of non-neutral binders (electrically charged) can present significant inhibitory results. 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 O4-N10. The molecule 2542 showed an inhibitory effect in two regions of interaction of the Tyr491-Glu37 site, acting on the BCPs H30-H33 and O8-H31 while the ligand 2600, in conformation 26, presented a similar effect only on the BCP O8-H31 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.