Tackling the SARS-CoV-2 main protease using hybrid derivatives of 1,5-disubstituted tetrazole-1,2,3-triazoles: an in silico assay

Tackling the SARS-CoV-2 main protease using hybrid derivatives of 1,5-disubstituted tetrazole-1,2,3-triazoles: an in silico assay

Luis Chacón-García, Erik Díaz-Cervantes, Carlos J. Cortes-García, Jorge Emmanuel Mejía-Benavides

In regard to the actual public health global emergency and, based on the state of the art about the ways to inhibit the SARS-CoV-2 treating the COVID19, a family of 1,5-disubstituted tetrazole-1,2,3-triazoles, previously synthesized, have been evaluated through in silico assays against the main protease of the mentioned virus (CoV-2-MPro). The results show that three of these compounds present a more favorable interaction with the selected target than the co-crystallized molecule, which is a peptide-like derivative. It was also found that also hydrophobic interactions play a key role in the ligand-target molecular couplings, due to the higher hydrophobic surfaces into the active site. Finally, a pharmacophore model has been proposed based on the results below, and a family of 1,5-DT derivatives has been designed and tested with the same methods employed in this work. It was concluded that the compound with the isatin as a substituent (P8) present the higher ligand-target interaction, which makes this a strong drug candidate against COVID19, due can inhibit the CoV-2-MPro protein.

2020

1, 2, 3-triazoles, pharmacophore model, SARS-CoV-2, COVID-19, 5-disubstituted-tetrazole-1, CoV-2-MPro, Docking-assays

DOI: 10.7717/peerj-pchem.10

PeerJ Physical Chemistry

PeerJ Inc.

Physical and theoretical chemistry