Virtual Screening of Repurposed Drugs as Potential Spike Protein Inhibitors of Different SARS-CoV-2 Variants: Molecular Docking Study
Like most of the RNA viruses, SARS-CoV-2 continuously mutates. Although many mutations have an insignificant impact on the virus properties, mutations in the surface protein, especially those in the receptor-binding domain, may lead to immune or vaccine escape variants, or altered binding activities...
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MDPI AG
2022-07-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/44/7/208 |
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| author | Ahmad F. Eweas Hosam-Eldin H. Osman Ibrahim A. Naguib Mohammed A. S. Abourehab Ahmed S. Abdel-Moneim |
| author_facet | Ahmad F. Eweas Hosam-Eldin H. Osman Ibrahim A. Naguib Mohammed A. S. Abourehab Ahmed S. Abdel-Moneim |
| author_sort | Ahmad F. Eweas |
| collection | DOAJ |
| description | Like most of the RNA viruses, SARS-CoV-2 continuously mutates. Although many mutations have an insignificant impact on the virus properties, mutations in the surface protein, especially those in the receptor-binding domain, may lead to immune or vaccine escape variants, or altered binding activities to both the cell receptor and the drugs targeting such a protein. The current study intended to assess the ability of different variants of interest (VOIs) and variants of concern (VOCs) of SARS-CoV-2 for their affinities of binding to different repurposed drugs. Seven FDA approved drugs, namely, camostat, nafamostat mesylate, fenofibrate, umifenovir, nelfinavir, cefoperazone and ceftazidime, were selected based on their reported in vitro and clinical activities against SARA-CoV-2. The S1 protein subunit from eleven different variants, including the latest highly contiguous omicron variant, were used as targets for the docking study. The docking results revealed that all tested drugs possess moderate to high binding energies to the receptor-binding domain (RBD) of the S1 protein for all different variants. Cefoperazone was found to possess the highest binding energy to the RBD of the S1 protein of all the eleven variants. Ceftazidime was the second-best drug in terms of binding affinity towards the S1 RBD of the investigated variants. On the other hand, fenofibrate showed the least binding affinity towards the RBD of the S1 protein of all eleven variants. The binding affinities of anti-spike drugs varied among different variants. Most of the interacting amino acid residues of the receptor fall within the RBD (438–506). |
| first_indexed | 2024-03-09T04:53:38Z |
| format | Article |
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| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-09T04:53:38Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Issues in Molecular Biology |
| spelling | doaj.art-07f0433aef8748efbb5f758fc6d351d12023-12-03T13:07:59ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452022-07-014473018302910.3390/cimb44070208Virtual Screening of Repurposed Drugs as Potential Spike Protein Inhibitors of Different SARS-CoV-2 Variants: Molecular Docking StudyAhmad F. Eweas0Hosam-Eldin H. Osman1Ibrahim A. Naguib2Mohammed A. S. Abourehab3Ahmed S. Abdel-Moneim4Department of Pharmaceutical and Medicinal Chemistry, National Research Centre, Cairo 12622, EgyptDepartment of Anatomy, College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi ArabiaDepartment of Microbiology, College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi ArabiaLike most of the RNA viruses, SARS-CoV-2 continuously mutates. Although many mutations have an insignificant impact on the virus properties, mutations in the surface protein, especially those in the receptor-binding domain, may lead to immune or vaccine escape variants, or altered binding activities to both the cell receptor and the drugs targeting such a protein. The current study intended to assess the ability of different variants of interest (VOIs) and variants of concern (VOCs) of SARS-CoV-2 for their affinities of binding to different repurposed drugs. Seven FDA approved drugs, namely, camostat, nafamostat mesylate, fenofibrate, umifenovir, nelfinavir, cefoperazone and ceftazidime, were selected based on their reported in vitro and clinical activities against SARA-CoV-2. The S1 protein subunit from eleven different variants, including the latest highly contiguous omicron variant, were used as targets for the docking study. The docking results revealed that all tested drugs possess moderate to high binding energies to the receptor-binding domain (RBD) of the S1 protein for all different variants. Cefoperazone was found to possess the highest binding energy to the RBD of the S1 protein of all the eleven variants. Ceftazidime was the second-best drug in terms of binding affinity towards the S1 RBD of the investigated variants. On the other hand, fenofibrate showed the least binding affinity towards the RBD of the S1 protein of all eleven variants. The binding affinities of anti-spike drugs varied among different variants. Most of the interacting amino acid residues of the receptor fall within the RBD (438–506).https://www.mdpi.com/1467-3045/44/7/208SARS-CoV-2VOCVOICOVID-19variantomicron |
| spellingShingle | Ahmad F. Eweas Hosam-Eldin H. Osman Ibrahim A. Naguib Mohammed A. S. Abourehab Ahmed S. Abdel-Moneim Virtual Screening of Repurposed Drugs as Potential Spike Protein Inhibitors of Different SARS-CoV-2 Variants: Molecular Docking Study Current Issues in Molecular Biology SARS-CoV-2 VOC VOI COVID-19 variant omicron |
| title | Virtual Screening of Repurposed Drugs as Potential Spike Protein Inhibitors of Different SARS-CoV-2 Variants: Molecular Docking Study |
| title_full | Virtual Screening of Repurposed Drugs as Potential Spike Protein Inhibitors of Different SARS-CoV-2 Variants: Molecular Docking Study |
| title_fullStr | Virtual Screening of Repurposed Drugs as Potential Spike Protein Inhibitors of Different SARS-CoV-2 Variants: Molecular Docking Study |
| title_full_unstemmed | Virtual Screening of Repurposed Drugs as Potential Spike Protein Inhibitors of Different SARS-CoV-2 Variants: Molecular Docking Study |
| title_short | Virtual Screening of Repurposed Drugs as Potential Spike Protein Inhibitors of Different SARS-CoV-2 Variants: Molecular Docking Study |
| title_sort | virtual screening of repurposed drugs as potential spike protein inhibitors of different sars cov 2 variants molecular docking study |
| topic | SARS-CoV-2 VOC VOI COVID-19 variant omicron |
| url | https://www.mdpi.com/1467-3045/44/7/208 |
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