Unlocking therapeutic potential: identifying small molecule inhibitors for SARSCOV-2 variants’ main protease (MPRO) through molecular docking analysis
Even with existing emergency drugs, the development of safer and more effective drugs for the treatment of COVID-19 still needs to continue. Virtual screening through a molecular docking approach is a powerful way to discover potential compounds for new drug discovery. In this study, we targeted SAR...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Penerbit Universiti Kebangsaan Malaysia
2024
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| Online Access: | http://journalarticle.ukm.my/24027/ http://journalarticle.ukm.my/24027/1/SEE%201.pdf |
| _version_ | 1848815995282522112 |
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| author | Chong, Yie Woon Nurul Izza Ismail, |
| author_facet | Chong, Yie Woon Nurul Izza Ismail, |
| author_sort | Chong, Yie Woon |
| building | UKM Institutional Repository |
| collection | Online Access |
| description | Even with existing emergency drugs, the development of safer and more effective drugs for the treatment of COVID-19 still needs to continue. Virtual screening through a molecular docking approach is a powerful way to discover potential compounds for new drug discovery. In this study, we targeted SARS-CoV-2 wild-type major protease (MPro), beta, lambda and omicron variants, to conduct a virtual screening with a selection of 100 ligands from the PubChem database using AutoDock Vina software. Among the inhibitors that have been identified are ten compounds consisting of ergotamine, 2,5-Dibenzyloxy-3-hydroxyligand-hexanedioic acid bis-[(2-hydroxy-indan-1-YL)-amide], remetinostat, benzamidine, argifin, irinotecan, dihydroergotamine, telmisartan, bromocriptine, and cilengitide, which exhibited the highest binding affinity. Interaction analysis through BIOVIA Discovery Studio showed the binding and interaction modes between these inhibitors and MPro residues of the variant. This mainly refers to 2,5-Dibenzyloxy-3-hydroxyligandhexanedioic acid bis-[(2-hydroxy-indan-1-YL)-amide] and remetinostat which consistently exhibit strong interactions with MPro variants. This research provides promising leads for the development of potential COVID-19 therapeutics. In summary, targeting conserved MPro with small molecule inhibitors provides a solid foundation for combating SARSCoV-2 and its variants, holding promise for effective COVID-19 mitigation. |
| first_indexed | 2025-11-15T00:58:50Z |
| format | Article |
| id | oai:generic.eprints.org:24027 |
| institution | Universiti Kebangasaan Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T00:58:50Z |
| publishDate | 2024 |
| publisher | Penerbit Universiti Kebangsaan Malaysia |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | oai:generic.eprints.org:240272024-08-23T08:03:41Z http://journalarticle.ukm.my/24027/ Unlocking therapeutic potential: identifying small molecule inhibitors for SARSCOV-2 variants’ main protease (MPRO) through molecular docking analysis Chong, Yie Woon Nurul Izza Ismail, Even with existing emergency drugs, the development of safer and more effective drugs for the treatment of COVID-19 still needs to continue. Virtual screening through a molecular docking approach is a powerful way to discover potential compounds for new drug discovery. In this study, we targeted SARS-CoV-2 wild-type major protease (MPro), beta, lambda and omicron variants, to conduct a virtual screening with a selection of 100 ligands from the PubChem database using AutoDock Vina software. Among the inhibitors that have been identified are ten compounds consisting of ergotamine, 2,5-Dibenzyloxy-3-hydroxyligand-hexanedioic acid bis-[(2-hydroxy-indan-1-YL)-amide], remetinostat, benzamidine, argifin, irinotecan, dihydroergotamine, telmisartan, bromocriptine, and cilengitide, which exhibited the highest binding affinity. Interaction analysis through BIOVIA Discovery Studio showed the binding and interaction modes between these inhibitors and MPro residues of the variant. This mainly refers to 2,5-Dibenzyloxy-3-hydroxyligandhexanedioic acid bis-[(2-hydroxy-indan-1-YL)-amide] and remetinostat which consistently exhibit strong interactions with MPro variants. This research provides promising leads for the development of potential COVID-19 therapeutics. In summary, targeting conserved MPro with small molecule inhibitors provides a solid foundation for combating SARSCoV-2 and its variants, holding promise for effective COVID-19 mitigation. Penerbit Universiti Kebangsaan Malaysia 2024 Article PeerReviewed application/pdf en http://journalarticle.ukm.my/24027/1/SEE%201.pdf Chong, Yie Woon and Nurul Izza Ismail, (2024) Unlocking therapeutic potential: identifying small molecule inhibitors for SARSCOV-2 variants’ main protease (MPRO) through molecular docking analysis. Sains Malaysiana, 53 (5). pp. 983-994. ISSN 0126-6039 https://www.ukm.my/jsm/english_journals/vol53num5_2024/contentsVol53num5_2024.html |
| spellingShingle | Chong, Yie Woon Nurul Izza Ismail, Unlocking therapeutic potential: identifying small molecule inhibitors for SARSCOV-2 variants’ main protease (MPRO) through molecular docking analysis |
| title | Unlocking therapeutic potential: identifying small molecule inhibitors for SARSCOV-2 variants’ main protease (MPRO) through molecular docking analysis |
| title_full | Unlocking therapeutic potential: identifying small molecule inhibitors for SARSCOV-2 variants’ main protease (MPRO) through molecular docking analysis |
| title_fullStr | Unlocking therapeutic potential: identifying small molecule inhibitors for SARSCOV-2 variants’ main protease (MPRO) through molecular docking analysis |
| title_full_unstemmed | Unlocking therapeutic potential: identifying small molecule inhibitors for SARSCOV-2 variants’ main protease (MPRO) through molecular docking analysis |
| title_short | Unlocking therapeutic potential: identifying small molecule inhibitors for SARSCOV-2 variants’ main protease (MPRO) through molecular docking analysis |
| title_sort | unlocking therapeutic potential: identifying small molecule inhibitors for sarscov-2 variants’ main protease (mpro) through molecular docking analysis |
| url | http://journalarticle.ukm.my/24027/ http://journalarticle.ukm.my/24027/ http://journalarticle.ukm.my/24027/1/SEE%201.pdf |