Integrated bioinformatics-cheminformatics approach toward locating pseudo-potential antiviral marine alkaloids against SARS-CoV-2-Mpro
© 2022 Wiley Periodicals LLC..
The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with the most contagious variants, alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2), and Omicron (B.1.1.529) has continuously added a higher number of morbidity and mortality, globally. The present integrated bioinformatics-cheminformatics approach was employed to locate potent antiviral marine alkaloids that could be used against SARS-CoV-2. Initially, 57 antiviral marine alkaloids and two repurposing drugs were selected from an extensive literature review. Then, the putative target enzyme SARS-CoV-2 main protease (SARS-CoV-2-Mpro) was retrieved from the protein data bank and carried out a virtual screening-cum-molecular docking study with all candidates using PyRx 0.8 and AutoDock 4.2 software. Further, the molecular dynamics (MD) simulation of the two most potential alkaloids and a drug docking complex at 100 ns (with two ligand topology files from PRODRG and ATB server, separately), the molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) free energy, and contributions of entropy were investigated. Then, the physicochemical-toxicity-pharmacokinetics-drug-likeness profiles, the frontier molecular orbitals energies (highest occupied molecular orbital, lowest unoccupied molecular orbital, and ΔE), and structural-activity relationship were assessed and analyzed. Based on binding energy, 8-hydroxymanzamine (-10.5 kcal/mol) and manzamine A (-10.1 kcal/mol) from all alkaloids with darunavir (-7.9 kcal/mol) and lopinavir (-7.4 kcal/mol) against SARS-CoV-2-Mpro were recorded. The MD simulation (RMSD, RMSF, Rg, H-bond, MM/PBSA binding energy) illustrated that the 8-hydroxymanzamine exhibits a static thermodynamic feature than the other two complexes. The predicted physicochemical, toxicity, pharmacokinetics, and drug-likeness profiles also revealed that the 8-hydroxymanzamine could be used as a potential lead candidate individually and/or synergistically with darunavir or lopinavir to combat SARS-CoV-2 infection after some pharmacological validation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:90 |
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| Enthalten in: |
Proteins - 90(2022), 9 vom: 20. Sept., Seite 1617-1633 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Swain, Shasank S [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.08.2022 Date Revised 07.12.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/prot.26341 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM339138238 |
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| 245 | 1 | 0 | |a Integrated bioinformatics-cheminformatics approach toward locating pseudo-potential antiviral marine alkaloids against SARS-CoV-2-Mpro |
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| 500 | |a Date Revised 07.12.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022 Wiley Periodicals LLC. | ||
| 520 | |a The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with the most contagious variants, alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2), and Omicron (B.1.1.529) has continuously added a higher number of morbidity and mortality, globally. The present integrated bioinformatics-cheminformatics approach was employed to locate potent antiviral marine alkaloids that could be used against SARS-CoV-2. Initially, 57 antiviral marine alkaloids and two repurposing drugs were selected from an extensive literature review. Then, the putative target enzyme SARS-CoV-2 main protease (SARS-CoV-2-Mpro) was retrieved from the protein data bank and carried out a virtual screening-cum-molecular docking study with all candidates using PyRx 0.8 and AutoDock 4.2 software. Further, the molecular dynamics (MD) simulation of the two most potential alkaloids and a drug docking complex at 100 ns (with two ligand topology files from PRODRG and ATB server, separately), the molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) free energy, and contributions of entropy were investigated. Then, the physicochemical-toxicity-pharmacokinetics-drug-likeness profiles, the frontier molecular orbitals energies (highest occupied molecular orbital, lowest unoccupied molecular orbital, and ΔE), and structural-activity relationship were assessed and analyzed. Based on binding energy, 8-hydroxymanzamine (-10.5 kcal/mol) and manzamine A (-10.1 kcal/mol) from all alkaloids with darunavir (-7.9 kcal/mol) and lopinavir (-7.4 kcal/mol) against SARS-CoV-2-Mpro were recorded. The MD simulation (RMSD, RMSF, Rg, H-bond, MM/PBSA binding energy) illustrated that the 8-hydroxymanzamine exhibits a static thermodynamic feature than the other two complexes. The predicted physicochemical, toxicity, pharmacokinetics, and drug-likeness profiles also revealed that the 8-hydroxymanzamine could be used as a potential lead candidate individually and/or synergistically with darunavir or lopinavir to combat SARS-CoV-2 infection after some pharmacological validation | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a drug-likeness profiles prediction | |
| 650 | 4 | |a molecular docking simulation | |
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| 650 | 7 | |a Alkaloids |2 NLM | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Protease Inhibitors |2 NLM | |
| 650 | 7 | |a Lopinavir |2 NLM | |
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| 700 | 1 | |a Sahoo, Alaka |e verfasserin |4 aut | |
| 700 | 1 | |a Panda, Pritam Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Hussain, Tahziba |e verfasserin |4 aut | |
| 700 | 1 | |a Pati, Sanghamitra |e verfasserin |4 aut | |
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