The objective of this work is to design new compounds more active against SARS-CoV-2. This design study of new inhibitors on the main protease source of coronavirus (3CLpro) was conducted on ten molecules using Molecular Modeling techniques (Docking, QSAR, ADMET). Molecular docking between M5, M8 and M1 showing best, medium and low scores respectively. The active site residues revealed that the M5 ligand establishes more hydrogen bonds on all the ligands studied thus forming the most stable complex. Predicting the pIC50 of the molecules in the training set as a function of the variation in binding energy (∆∆G) to the pathogen, allowed us to develop a QSAR model accredited with very good statistical indicators R2 = 0.9137; S = 0.058; F = 52.942. The applicability domain of the model obtained from the lever method shows that all compounds belong to the applicability domain. Moreover, the reliability of this model allowed the design of twenty (20) new potential molecules with theoretical inhibitory concentration potentials (pIC50th) values superior to those of the molecules in the database. Finally, the pharmacokinetic profile of the proposed molecules was confirmed by the satisfaction of the Lipinski and ADMET.
| Published in | Modern Chemistry (Volume 10, Issue 2) |
| DOI | 10.11648/j.mc.20221002.12 |
| Page(s) | 30-47 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
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Copyright © The Author(s), 2022. Published by Science Publishing Group |
SARS-CoV-2, QSAR, Docking, ADMET
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APA Style
Georges Stéphane Dembélé, Mamadou Guy-Richard Koné, Doh Soro, Fandia Konaté, Bibata Konaté, et al. (2022). Design of New Inhibitors to Fight Against the 3CLpro Protease of SARS-CoV-2 (COVID-19). Modern Chemistry, 10(2), 30-47. https://doi.org/10.11648/j.mc.20221002.12
ACS Style
Georges Stéphane Dembélé; Mamadou Guy-Richard Koné; Doh Soro; Fandia Konaté; Bibata Konaté, et al. Design of New Inhibitors to Fight Against the 3CLpro Protease of SARS-CoV-2 (COVID-19). Mod. Chem. 2022, 10(2), 30-47. doi: 10.11648/j.mc.20221002.12
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Download@article{10.11648/j.mc.20221002.12,
author = {Georges Stéphane Dembélé and Mamadou Guy-Richard Koné and Doh Soro and Fandia Konaté and Bibata Konaté and Nahossé Ziao},
title = {Design of New Inhibitors to Fight Against the 3CLpro Protease of SARS-CoV-2 (COVID-19)},
journal = {Modern Chemistry},
volume = {10},
number = {2},
pages = {30-47},
doi = {10.11648/j.mc.20221002.12},
url = {https://doi.org/10.11648/j.mc.20221002.12},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.mc.20221002.12},
abstract = {The objective of this work is to design new compounds more active against SARS-CoV-2. This design study of new inhibitors on the main protease source of coronavirus (3CLpro) was conducted on ten molecules using Molecular Modeling techniques (Docking, QSAR, ADMET). Molecular docking between M5, M8 and M1 showing best, medium and low scores respectively. The active site residues revealed that the M5 ligand establishes more hydrogen bonds on all the ligands studied thus forming the most stable complex. Predicting the pIC50 of the molecules in the training set as a function of the variation in binding energy (∆∆G) to the pathogen, allowed us to develop a QSAR model accredited with very good statistical indicators R2 = 0.9137; S = 0.058; F = 52.942. The applicability domain of the model obtained from the lever method shows that all compounds belong to the applicability domain. Moreover, the reliability of this model allowed the design of twenty (20) new potential molecules with theoretical inhibitory concentration potentials (pIC50th) values superior to those of the molecules in the database. Finally, the pharmacokinetic profile of the proposed molecules was confirmed by the satisfaction of the Lipinski and ADMET.},
year = {2022}
}
TY - JOUR T1 - Design of New Inhibitors to Fight Against the 3CLpro Protease of SARS-CoV-2 (COVID-19) AU - Georges Stéphane Dembélé AU - Mamadou Guy-Richard Koné AU - Doh Soro AU - Fandia Konaté AU - Bibata Konaté AU - Nahossé Ziao Y1 - 2022/04/28 PY - 2022 N1 - https://doi.org/10.11648/j.mc.20221002.12 DO - 10.11648/j.mc.20221002.12 T2 - Modern Chemistry JF - Modern Chemistry JO - Modern Chemistry SP - 30 EP - 47 PB - Science Publishing Group SN - 2329-180X UR - https://doi.org/10.11648/j.mc.20221002.12 AB - The objective of this work is to design new compounds more active against SARS-CoV-2. This design study of new inhibitors on the main protease source of coronavirus (3CLpro) was conducted on ten molecules using Molecular Modeling techniques (Docking, QSAR, ADMET). Molecular docking between M5, M8 and M1 showing best, medium and low scores respectively. The active site residues revealed that the M5 ligand establishes more hydrogen bonds on all the ligands studied thus forming the most stable complex. Predicting the pIC50 of the molecules in the training set as a function of the variation in binding energy (∆∆G) to the pathogen, allowed us to develop a QSAR model accredited with very good statistical indicators R2 = 0.9137; S = 0.058; F = 52.942. The applicability domain of the model obtained from the lever method shows that all compounds belong to the applicability domain. Moreover, the reliability of this model allowed the design of twenty (20) new potential molecules with theoretical inhibitory concentration potentials (pIC50th) values superior to those of the molecules in the database. Finally, the pharmacokinetic profile of the proposed molecules was confirmed by the satisfaction of the Lipinski and ADMET. VL - 10 IS - 2 ER -
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