In Silico Study of Coumarins: Wedelolactone as a Potential Inhibitor of the Spike Protein of the SARS-CoV-2 Variants
Despite the rigorous global efforts to control SARS-CoV-2 transmission, it continues to pose a serious threat to humans with the frequent emergence of new variants. Thus, robust therapeutics to combat the virus are a desperate need. The SARS-CoV-2 spike (S) protein is an important target protein as...
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | Journal of Tropical Medicine |
| Online Access: | http://dx.doi.org/10.1155/2023/4771745 |
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| author | Saurav Katuwal Siddha Raj Upadhyaya Rishab Marahatha Asmita Shrestha Bishnu P. Regmi Karan Khadayat Saroj Basnet Ram Chandra Basnyat Niranjan Parajuli |
| author_facet | Saurav Katuwal Siddha Raj Upadhyaya Rishab Marahatha Asmita Shrestha Bishnu P. Regmi Karan Khadayat Saroj Basnet Ram Chandra Basnyat Niranjan Parajuli |
| author_sort | Saurav Katuwal |
| collection | DOAJ |
| description | Despite the rigorous global efforts to control SARS-CoV-2 transmission, it continues to pose a serious threat to humans with the frequent emergence of new variants. Thus, robust therapeutics to combat the virus are a desperate need. The SARS-CoV-2 spike (S) protein is an important target protein as it mediates the entry of the virus inside the host cells, which is initiated by the binding of the receptor-binding domain (RBD) to its cognate receptor, angiotensin-converting enzyme 2 (ACE-2). Herein, the inhibition potential of several naturally occurring coumarins was investigated against the spike proteins of SARS-CoV-2 variants using computational approaches. Molecular docking studies revealed 26 coumarins with better binding energies than the reference ligands, molnupiravir and ceftazidime, against the S-RBD of the omicron variant. The top 10 best-docked coumarins were further analyzed to understand their binding interactions against the spike proteins of other variants (wild-type, Alpha, Beta, Gamma, and Delta), and these studies also demonstrated decent binding energies. Physicochemical, QSAR, and pharmacokinetics analyses of the coumarins revealed wedelolactone as the best inhibitor of the spike protein with ideal Lipinski’s drug-likeness and optimal ADMET properties. Furthermore, coarse-grained molecular dynamics (MD) simulation studies of spike protein-wedelolactone complexes validated the stable binding of wedelolactone in the respective binding pockets. As an outcome, wedelolactone could be utilized to develop a potent drug candidate against COVID-19 by blocking the viral entry into the host cell. |
| format | Article |
| id | doaj-art-a8f6faabd9b9458790e6dbf83c175e7c |
| institution | Kabale University |
| issn | 1687-9694 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Tropical Medicine |
| spelling | doaj-art-a8f6faabd9b9458790e6dbf83c175e7c2025-02-03T10:25:25ZengWileyJournal of Tropical Medicine1687-96942023-01-01202310.1155/2023/4771745In Silico Study of Coumarins: Wedelolactone as a Potential Inhibitor of the Spike Protein of the SARS-CoV-2 VariantsSaurav Katuwal0Siddha Raj Upadhyaya1Rishab Marahatha2Asmita Shrestha3Bishnu P. Regmi4Karan Khadayat5Saroj Basnet6Ram Chandra Basnyat7Niranjan Parajuli8Central Department of ChemistryCentral Department of ChemistryCentral Department of ChemistryCentral Department of ChemistryDepartment of ChemistryCentral Department of ChemistryCenter for Drug Design and Molecular Simulation DivisionCentral Department of ChemistryCentral Department of ChemistryDespite the rigorous global efforts to control SARS-CoV-2 transmission, it continues to pose a serious threat to humans with the frequent emergence of new variants. Thus, robust therapeutics to combat the virus are a desperate need. The SARS-CoV-2 spike (S) protein is an important target protein as it mediates the entry of the virus inside the host cells, which is initiated by the binding of the receptor-binding domain (RBD) to its cognate receptor, angiotensin-converting enzyme 2 (ACE-2). Herein, the inhibition potential of several naturally occurring coumarins was investigated against the spike proteins of SARS-CoV-2 variants using computational approaches. Molecular docking studies revealed 26 coumarins with better binding energies than the reference ligands, molnupiravir and ceftazidime, against the S-RBD of the omicron variant. The top 10 best-docked coumarins were further analyzed to understand their binding interactions against the spike proteins of other variants (wild-type, Alpha, Beta, Gamma, and Delta), and these studies also demonstrated decent binding energies. Physicochemical, QSAR, and pharmacokinetics analyses of the coumarins revealed wedelolactone as the best inhibitor of the spike protein with ideal Lipinski’s drug-likeness and optimal ADMET properties. Furthermore, coarse-grained molecular dynamics (MD) simulation studies of spike protein-wedelolactone complexes validated the stable binding of wedelolactone in the respective binding pockets. As an outcome, wedelolactone could be utilized to develop a potent drug candidate against COVID-19 by blocking the viral entry into the host cell.http://dx.doi.org/10.1155/2023/4771745 |
| spellingShingle | Saurav Katuwal Siddha Raj Upadhyaya Rishab Marahatha Asmita Shrestha Bishnu P. Regmi Karan Khadayat Saroj Basnet Ram Chandra Basnyat Niranjan Parajuli In Silico Study of Coumarins: Wedelolactone as a Potential Inhibitor of the Spike Protein of the SARS-CoV-2 Variants Journal of Tropical Medicine |
| title | In Silico Study of Coumarins: Wedelolactone as a Potential Inhibitor of the Spike Protein of the SARS-CoV-2 Variants |
| title_full | In Silico Study of Coumarins: Wedelolactone as a Potential Inhibitor of the Spike Protein of the SARS-CoV-2 Variants |
| title_fullStr | In Silico Study of Coumarins: Wedelolactone as a Potential Inhibitor of the Spike Protein of the SARS-CoV-2 Variants |
| title_full_unstemmed | In Silico Study of Coumarins: Wedelolactone as a Potential Inhibitor of the Spike Protein of the SARS-CoV-2 Variants |
| title_short | In Silico Study of Coumarins: Wedelolactone as a Potential Inhibitor of the Spike Protein of the SARS-CoV-2 Variants |
| title_sort | in silico study of coumarins wedelolactone as a potential inhibitor of the spike protein of the sars cov 2 variants |
| url | http://dx.doi.org/10.1155/2023/4771745 |
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