In Silico Screening of Semi-Synthesized Compounds as Potential Inhibitors for SARS-CoV-2 Papain-like Protease: Pharmacophoric Features, Molecular Docking, ADMET, Toxicity and DFT Studies DOI Creative Commons
Mohamed S. Alesawy, Eslam B. Elkaeed, Aisha A. Alsfouk

et al.

Molecules, Journal Year: 2021, Volume and Issue: 26(21), P. 6593 - 6593

Published: Oct. 30, 2021

Papain-like protease is an essential enzyme in the proteolytic processing required for replication of SARS-CoV-2. Accordingly, such important target development anti-SARS-CoV-2 agents which may reduce mortality associated with outbreaks A set 69 semi-synthesized molecules that exhibited structural features SARS-CoV-2 papain-like inhibitors (PLPI) were docked against coronavirus (PLpro) (PDB ID: (4OW0). Docking studies showed derivatives 34 and 58 better than co-crystallized ligand while 17, 28, 31, 40, 41, 43, 47, 54, 65 good binding modes free energies. The pharmacokinetic profiling study was conducted according to four principles Lipinski rules excluded derivative 31. Furthermore, ADMET toxicity 34, 47 have potential be drugs been demonstrated as safe when assessed via seven models. Finally, comparing molecular orbital energies electrostatic maps a DFT indicated 28 most promising candidate interact receptor (PLpro).

Language: Английский

Computer-aided drug discovery of natural antiviral metabolites as potential SARS-CoV-2 helicase inhibitors DOI Creative Commons
Eslam B. Elkaeed, Ibrahim H. Eissa, Abdulrahman M. Saleh

et al.

Journal of Chemical Research, Journal Year: 2024, Volume and Issue: 48(1)

Published: Jan. 1, 2024

In our quest to discover effective inhibitors against severe acute respiratory syndrome coronavirus 2 helicase, a diverse set of more than 300 naturally occurring antiviral metabolites was investigated. Employing advanced computational techniques, we initiated the selection process by analyzing and comparing co-crystallized ligand (VXG) helicase protein (PDB ID: 5RMM) identify compounds with structurally similar features potential for comparable binding. Through structural similarity pharmacophore research, 13 that shared important characteristics VXG were pinpointed. Subsequently, these candidates subjected molecular docking seven demonstrated favorable energy profiles accurate binding helicase. Among these, mycophenolic acid emerged as most promising candidate. To ensure safety viability selected compounds, conducted ADMET tests, which confirmed acid, atropine plumbagin. Building on results, performed additional analyses including various dynamics simulations. These investigations exhibited optimal maintaining flawless throughout Furthermore, Molecular Mechanics Poisson–Boltzmann Surface Area tests provided strong evidence successfully formed stable connection calculated free value −294 kJ mol −1 . encouraging findings provide solid foundation further in vitro vivo studies, three identified compounds. The efficacy treatment options coronavirus-19 warrants exploration may hold significant promise ongoing fight pandemic.

Language: Английский

Citations

8
Recent Advances and Future Directions on Small Molecule VEGFR Inhibitors in Oncological Conditions DOI

Amandeep Thakur,

Mandeep Rana,

Anshul Mishra

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 272, P. 116472 - 116472

Published: May 6, 2024

Language: Английский

Citations

8
Design and synthesis of new 4-(2-nitrophenoxy)benzamide derivatives as potential antiviral agents: molecular modeling and in vitro antiviral screening DOI
Abdallah E. Abdallah, Mohamed S. Alesawy, Sally I. Eissa

et al.

New Journal of Chemistry, Journal Year: 2021, Volume and Issue: 45(36), P. 16557 - 16571

Published: Jan. 1, 2021

Novel benzamide derivatives as anti adenovirus, HSV-1, coxsackievirus, and SARS-CoV-2: in vitro silico study.

Language: Английский

Citations

55
In Silico Exploration of Potential Natural Inhibitors against SARS-Cov-2 nsp10 DOI Creative Commons
Ibrahim H. Eissa, Mohamed M. Khalifa, Eslam B. Elkaeed

et al.

Molecules, Journal Year: 2021, Volume and Issue: 26(20), P. 6151 - 6151

Published: Oct. 12, 2021

In continuation of our previous effort, different in silico selection methods were applied to 310 naturally isolated metabolites that exhibited antiviral potentialities before. The aimed pick the most relevant inhibitor SARS-CoV-2 nsp10. At first, a structural similarity study against co-crystallized ligand, S-Adenosyl Methionine (SAM), nonstructural protein (nsp10) (PDB ID: 6W4H) was carried out. analysis culled 30 candidates. Secondly, fingerprint SAM preferred compounds 44, 48, 85, 102, 105, 182, 220, 221, 282, 284, 285, 301, and 302. docking studies picked 284. While ADMET expected likeness five candidates be drugs, toxicity 48 182. Finally, density-functional theory (DFT) suggested vidarabine (182) SARS-Cov-2 nsp10 inhibitor.

Language: Английский

Citations

54
In Silico Screening of Semi-Synthesized Compounds as Potential Inhibitors for SARS-CoV-2 Papain-like Protease: Pharmacophoric Features, Molecular Docking, ADMET, Toxicity and DFT Studies DOI Creative Commons
Mohamed S. Alesawy, Eslam B. Elkaeed, Aisha A. Alsfouk

et al.

Molecules, Journal Year: 2021, Volume and Issue: 26(21), P. 6593 - 6593

Published: Oct. 30, 2021

Papain-like protease is an essential enzyme in the proteolytic processing required for replication of SARS-CoV-2. Accordingly, such important target development anti-SARS-CoV-2 agents which may reduce mortality associated with outbreaks A set 69 semi-synthesized molecules that exhibited structural features SARS-CoV-2 papain-like inhibitors (PLPI) were docked against coronavirus (PLpro) (PDB ID: (4OW0). Docking studies showed derivatives 34 and 58 better than co-crystallized ligand while 17, 28, 31, 40, 41, 43, 47, 54, 65 good binding modes free energies. The pharmacokinetic profiling study was conducted according to four principles Lipinski rules excluded derivative 31. Furthermore, ADMET toxicity 34, 47 have potential be drugs been demonstrated as safe when assessed via seven models. Finally, comparing molecular orbital energies electrostatic maps a DFT indicated 28 most promising candidate interact receptor (PLpro).

Language: Английский

Citations

46