QSAR based virtual screening derived identification of a novel hit as a SARS CoV-229E 3CLpro Inhibitor: GA-MLR QSAR modeling supported by molecular Docking, molecular dynamics simulation and MMGBSA calculation approaches

Congruous coronavirus drug targets and analogous lead molecules must be identified as quickly as possible to produce antiviral therapeutics against human coronavirus (HCoV SARS 3CLpro) infections. In the present communication, we bear recognized a HIT candidate for HCoV SARS 3CLpro inhibition. Four...

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Autores principales:	R.D. Jawarkar, Ravindrakumar L. Bakal, Magdi E.A. Zaki, Sami Al-Hussain, Arabinda Ghosh, Ajaykumar Gandhi, Nobendu Mukerjee, Abdul Samad, Vijay H. Masand, Israa Lewaa
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	HCoV SARS 3CLpro GA-MLR QSAR based virtual screening Molecular docking and MD simulation Lead MMGBSA calculations Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/7b0fa53898a344f9a4ccc41cbe5d2f9b
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spelling	oai:doaj.org-article:7b0fa53898a344f9a4ccc41cbe5d2f9b2021-11-04T04:27:44ZQSAR based virtual screening derived identification of a novel hit as a SARS CoV-229E 3CLpro Inhibitor: GA-MLR QSAR modeling supported by molecular Docking, molecular dynamics simulation and MMGBSA calculation approaches1878-535210.1016/j.arabjc.2021.103499https://doaj.org/article/7b0fa53898a344f9a4ccc41cbe5d2f9b2022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1878535221005141https://doaj.org/toc/1878-5352Congruous coronavirus drug targets and analogous lead molecules must be identified as quickly as possible to produce antiviral therapeutics against human coronavirus (HCoV SARS 3CLpro) infections. In the present communication, we bear recognized a HIT candidate for HCoV SARS 3CLpro inhibition. Four Parametric GA-MLR primarily based QSAR model (R2:0.84, R2adj:0.82, Q2loo: 0.78) was once promoted using a dataset over 37 structurally diverse molecules along QSAR based virtual screening (QSAR-VS), molecular docking (MD) then molecular dynamic simulation (MDS) analysis and MMGBSA calculations. The QSAR-based virtual screening was utilized to find novel lead molecules from an in-house database of 100 molecules. The QSAR-vS successfully offered a hit molecule with an improved PEC50 value from 5.88 to 6.08. The benzene ring, phenyl ring, amide oxygen and nitrogen, and other important pharmacophoric sites are revealed via MD and MDS studies. Ile164, Pro188, Leu190, Thr25, His41, Asn46, Thr47, Ser49, Asn189, Gln191, Thr47, and Asn141 are among the key amino acid residues in the S1 and S2 pocket. A stable complex of a lead molecule with the HCoV SARS 3CLpro was discovered using MDS. MM-GBSA calculations resulted from MD simulation results well supported with the binding energies calculated from the docking results. The results of this study can be exploited to develop a novel antiviral target, such as an HCoV SARS 3CLpro Inhibitor.R.D. JawarkarRavindrakumar L. BakalMagdi E.A. ZakiSami Al-HussainArabinda GhoshAjaykumar GandhiNobendu MukerjeeAbdul SamadVijay H. MasandIsraa LewaaElsevierarticleHCoV SARS 3CLproGA-MLRQSAR based virtual screeningMolecular docking and MD simulationLeadMMGBSA calculationsChemistryQD1-999ENArabian Journal of Chemistry, Vol 15, Iss 1, Pp 103499- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	HCoV SARS 3CLpro GA-MLR QSAR based virtual screening Molecular docking and MD simulation Lead MMGBSA calculations Chemistry QD1-999
spellingShingle	HCoV SARS 3CLpro GA-MLR QSAR based virtual screening Molecular docking and MD simulation Lead MMGBSA calculations Chemistry QD1-999 R.D. Jawarkar Ravindrakumar L. Bakal Magdi E.A. Zaki Sami Al-Hussain Arabinda Ghosh Ajaykumar Gandhi Nobendu Mukerjee Abdul Samad Vijay H. Masand Israa Lewaa QSAR based virtual screening derived identification of a novel hit as a SARS CoV-229E 3CLpro Inhibitor: GA-MLR QSAR modeling supported by molecular Docking, molecular dynamics simulation and MMGBSA calculation approaches
description	Congruous coronavirus drug targets and analogous lead molecules must be identified as quickly as possible to produce antiviral therapeutics against human coronavirus (HCoV SARS 3CLpro) infections. In the present communication, we bear recognized a HIT candidate for HCoV SARS 3CLpro inhibition. Four Parametric GA-MLR primarily based QSAR model (R2:0.84, R2adj:0.82, Q2loo: 0.78) was once promoted using a dataset over 37 structurally diverse molecules along QSAR based virtual screening (QSAR-VS), molecular docking (MD) then molecular dynamic simulation (MDS) analysis and MMGBSA calculations. The QSAR-based virtual screening was utilized to find novel lead molecules from an in-house database of 100 molecules. The QSAR-vS successfully offered a hit molecule with an improved PEC50 value from 5.88 to 6.08. The benzene ring, phenyl ring, amide oxygen and nitrogen, and other important pharmacophoric sites are revealed via MD and MDS studies. Ile164, Pro188, Leu190, Thr25, His41, Asn46, Thr47, Ser49, Asn189, Gln191, Thr47, and Asn141 are among the key amino acid residues in the S1 and S2 pocket. A stable complex of a lead molecule with the HCoV SARS 3CLpro was discovered using MDS. MM-GBSA calculations resulted from MD simulation results well supported with the binding energies calculated from the docking results. The results of this study can be exploited to develop a novel antiviral target, such as an HCoV SARS 3CLpro Inhibitor.
format	article
author	R.D. Jawarkar Ravindrakumar L. Bakal Magdi E.A. Zaki Sami Al-Hussain Arabinda Ghosh Ajaykumar Gandhi Nobendu Mukerjee Abdul Samad Vijay H. Masand Israa Lewaa
author_facet	R.D. Jawarkar Ravindrakumar L. Bakal Magdi E.A. Zaki Sami Al-Hussain Arabinda Ghosh Ajaykumar Gandhi Nobendu Mukerjee Abdul Samad Vijay H. Masand Israa Lewaa
author_sort	R.D. Jawarkar
title	QSAR based virtual screening derived identification of a novel hit as a SARS CoV-229E 3CLpro Inhibitor: GA-MLR QSAR modeling supported by molecular Docking, molecular dynamics simulation and MMGBSA calculation approaches
title_short	QSAR based virtual screening derived identification of a novel hit as a SARS CoV-229E 3CLpro Inhibitor: GA-MLR QSAR modeling supported by molecular Docking, molecular dynamics simulation and MMGBSA calculation approaches
title_full	QSAR based virtual screening derived identification of a novel hit as a SARS CoV-229E 3CLpro Inhibitor: GA-MLR QSAR modeling supported by molecular Docking, molecular dynamics simulation and MMGBSA calculation approaches
title_fullStr	QSAR based virtual screening derived identification of a novel hit as a SARS CoV-229E 3CLpro Inhibitor: GA-MLR QSAR modeling supported by molecular Docking, molecular dynamics simulation and MMGBSA calculation approaches
title_full_unstemmed	QSAR based virtual screening derived identification of a novel hit as a SARS CoV-229E 3CLpro Inhibitor: GA-MLR QSAR modeling supported by molecular Docking, molecular dynamics simulation and MMGBSA calculation approaches
title_sort	qsar based virtual screening derived identification of a novel hit as a sars cov-229e 3clpro inhibitor: ga-mlr qsar modeling supported by molecular docking, molecular dynamics simulation and mmgbsa calculation approaches
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/7b0fa53898a344f9a4ccc41cbe5d2f9b
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QSAR based virtual screening derived identification of a novel hit as a SARS CoV-229E 3CLpro Inhibitor: GA-MLR QSAR modeling supported by molecular Docking, molecular dynamics simulation and MMGBSA calculation approaches

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