Ligand and Structure-Based In Silico Determination of the Most Promising SARS-CoV-2 nsp16-nsp10 2′-<i>o</i>-Methyltransferase Complex Inhibitors among 3009 FDA Approved Drugs
As a continuation of our earlier work against SARS-CoV-2, seven FDA-approved drugs were designated as the best SARS-CoV-2 nsp16-nsp10 2′-<i>o</i>-methyltransferase (2′OMTase) inhibitors through 3009 compounds. The in silico inhibitory potential of the examined compounds against SARS-CoV-...
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MDPI AG
2022-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/7/2287 |
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| author | Ibrahim H. Eissa Mohamed S. Alesawy Abdulrahman M. Saleh Eslam B. Elkaeed Bshra A. Alsfouk Abdul-Aziz M. M. El-Attar Ahmed M. Metwaly |
| author_facet | Ibrahim H. Eissa Mohamed S. Alesawy Abdulrahman M. Saleh Eslam B. Elkaeed Bshra A. Alsfouk Abdul-Aziz M. M. El-Attar Ahmed M. Metwaly |
| author_sort | Ibrahim H. Eissa |
| collection | DOAJ |
| description | As a continuation of our earlier work against SARS-CoV-2, seven FDA-approved drugs were designated as the best SARS-CoV-2 nsp16-nsp10 2′-<i>o</i>-methyltransferase (2′OMTase) inhibitors through 3009 compounds. The in silico inhibitory potential of the examined compounds against SARS-CoV-2 nsp16-nsp10 2′-<i>o</i>-methyltransferase (PDB ID: (6W4H) was conducted through a multi-step screening approach. At the beginning, molecular fingerprints experiment with <b>SAM</b> (<i>S</i>-Adenosylmethionine), the co-crystallized ligand of the targeted enzyme, unveiled the resemblance of 147 drugs. Then, a structural similarity experiment recommended 26 compounds. Therefore, the 26 compounds were docked against 2′OMTase to reveal the potential inhibitory effect of seven promising compounds (Protirelin, (<b>1187</b>), Calcium folinate (<b>1913</b>), Raltegravir (<b>1995</b>), Regadenoson (<b>2176</b>), Ertapenem (<b>2396</b>), Methylergometrine (<b>2532</b>), and Thiamine pyrophosphate hydrochloride (<b>2612</b>)). Out of the docked ligands, Ertapenem (<b>2396</b>) showed an ideal binding mode like that of the co-crystallized ligand (<b>SAM</b>). It occupied all sub-pockets of the active site and bound the crucial amino acids. Accordingly, some MD simulation experiments (RMSD, RMSF, R<sub>g</sub>, SASA, and H-bonding) have been conducted for the 2′OMTase—Ertapenem complex over 100 ns. The performed MD experiments verified the correct binding mode of Ertapenem against 2′OMTase exhibiting low energy and optimal dynamics. Finally, MM-PBSA studies indicated that Ertapenem bonded advantageously to the targeted protein with a free energy value of −43 KJ/mol. Furthermore, the binding free energy analysis revealed the essential amino acids of 2′OMTase that served positively to the binding. The achieved results bring hope to find a treatment for COVID-19 via in vitro and in vivo studies for the pointed compounds. |
| first_indexed | 2024-03-09T11:35:35Z |
| format | Article |
| id | doaj.art-11099f2b903f4fe986860786e2f0ac45 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T11:35:35Z |
| publishDate | 2022-03-01 |
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| spelling | doaj.art-11099f2b903f4fe986860786e2f0ac452023-11-30T23:42:10ZengMDPI AGMolecules1420-30492022-03-01277228710.3390/molecules27072287Ligand and Structure-Based In Silico Determination of the Most Promising SARS-CoV-2 nsp16-nsp10 2′-<i>o</i>-Methyltransferase Complex Inhibitors among 3009 FDA Approved DrugsIbrahim H. Eissa0Mohamed S. Alesawy1Abdulrahman M. Saleh2Eslam B. Elkaeed3Bshra A. Alsfouk4Abdul-Aziz M. M. El-Attar5Ahmed M. Metwaly6Pharmaceutical Medicinal Chemistry and Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, EgyptPharmaceutical Medicinal Chemistry and Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, EgyptPharmaceutical Medicinal Chemistry and Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, EgyptDepartment of Pharmaceutical Sciences, College of Pharmacy, Almaarefa University, Riyadh 13713, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi ArabiaPharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, EgyptPharmacognosy and Medicinal Plants Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, EgyptAs a continuation of our earlier work against SARS-CoV-2, seven FDA-approved drugs were designated as the best SARS-CoV-2 nsp16-nsp10 2′-<i>o</i>-methyltransferase (2′OMTase) inhibitors through 3009 compounds. The in silico inhibitory potential of the examined compounds against SARS-CoV-2 nsp16-nsp10 2′-<i>o</i>-methyltransferase (PDB ID: (6W4H) was conducted through a multi-step screening approach. At the beginning, molecular fingerprints experiment with <b>SAM</b> (<i>S</i>-Adenosylmethionine), the co-crystallized ligand of the targeted enzyme, unveiled the resemblance of 147 drugs. Then, a structural similarity experiment recommended 26 compounds. Therefore, the 26 compounds were docked against 2′OMTase to reveal the potential inhibitory effect of seven promising compounds (Protirelin, (<b>1187</b>), Calcium folinate (<b>1913</b>), Raltegravir (<b>1995</b>), Regadenoson (<b>2176</b>), Ertapenem (<b>2396</b>), Methylergometrine (<b>2532</b>), and Thiamine pyrophosphate hydrochloride (<b>2612</b>)). Out of the docked ligands, Ertapenem (<b>2396</b>) showed an ideal binding mode like that of the co-crystallized ligand (<b>SAM</b>). It occupied all sub-pockets of the active site and bound the crucial amino acids. Accordingly, some MD simulation experiments (RMSD, RMSF, R<sub>g</sub>, SASA, and H-bonding) have been conducted for the 2′OMTase—Ertapenem complex over 100 ns. The performed MD experiments verified the correct binding mode of Ertapenem against 2′OMTase exhibiting low energy and optimal dynamics. Finally, MM-PBSA studies indicated that Ertapenem bonded advantageously to the targeted protein with a free energy value of −43 KJ/mol. Furthermore, the binding free energy analysis revealed the essential amino acids of 2′OMTase that served positively to the binding. The achieved results bring hope to find a treatment for COVID-19 via in vitro and in vivo studies for the pointed compounds.https://www.mdpi.com/1420-3049/27/7/2287SARS-CoV-2 nsp16-nsp10 2′-<i>o</i>-methyltransferaseFDA approved drugsmolecular fingerprintsstructural similaritymolecular dockingMD simulations |
| spellingShingle | Ibrahim H. Eissa Mohamed S. Alesawy Abdulrahman M. Saleh Eslam B. Elkaeed Bshra A. Alsfouk Abdul-Aziz M. M. El-Attar Ahmed M. Metwaly Ligand and Structure-Based In Silico Determination of the Most Promising SARS-CoV-2 nsp16-nsp10 2′-<i>o</i>-Methyltransferase Complex Inhibitors among 3009 FDA Approved Drugs Molecules SARS-CoV-2 nsp16-nsp10 2′-<i>o</i>-methyltransferase FDA approved drugs molecular fingerprints structural similarity molecular docking MD simulations |
| title | Ligand and Structure-Based In Silico Determination of the Most Promising SARS-CoV-2 nsp16-nsp10 2′-<i>o</i>-Methyltransferase Complex Inhibitors among 3009 FDA Approved Drugs |
| title_full | Ligand and Structure-Based In Silico Determination of the Most Promising SARS-CoV-2 nsp16-nsp10 2′-<i>o</i>-Methyltransferase Complex Inhibitors among 3009 FDA Approved Drugs |
| title_fullStr | Ligand and Structure-Based In Silico Determination of the Most Promising SARS-CoV-2 nsp16-nsp10 2′-<i>o</i>-Methyltransferase Complex Inhibitors among 3009 FDA Approved Drugs |
| title_full_unstemmed | Ligand and Structure-Based In Silico Determination of the Most Promising SARS-CoV-2 nsp16-nsp10 2′-<i>o</i>-Methyltransferase Complex Inhibitors among 3009 FDA Approved Drugs |
| title_short | Ligand and Structure-Based In Silico Determination of the Most Promising SARS-CoV-2 nsp16-nsp10 2′-<i>o</i>-Methyltransferase Complex Inhibitors among 3009 FDA Approved Drugs |
| title_sort | ligand and structure based in silico determination of the most promising sars cov 2 nsp16 nsp10 2 i o i methyltransferase complex inhibitors among 3009 fda approved drugs |
| topic | SARS-CoV-2 nsp16-nsp10 2′-<i>o</i>-methyltransferase FDA approved drugs molecular fingerprints structural similarity molecular docking MD simulations |
| url | https://www.mdpi.com/1420-3049/27/7/2287 |
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