Lead compound discovery using pharmacophore-based models of small-molecule metabolites from human blood as inhibitor cellular entry of SARS-CoV-2
Context: The development of emerging viral diseases like SARS-CoV-2 has underlined the critical need for new antiviral medicines. Many of the discovered inhibitors have off-target effects or toxicity issues, but no single lead chemical has been found as a powerful SARS-CoV-2 inhibitor. Small-molecul...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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GarVal Editorial Ltda.
2023-09-01
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| Series: | Journal of Pharmacy & Pharmacognosy Research |
| Subjects: | |
| Online Access: | https://jppres.com/jppres/pdf/vol11/jppres23.1688_11.5.810.pdf |
| _version_ | 1797682556262416384 |
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| author | Ellin Febrina Aiyi Asnawi |
| author_facet | Ellin Febrina Aiyi Asnawi |
| author_sort | Ellin Febrina |
| collection | DOAJ |
| description | Context: The development of emerging viral diseases like SARS-CoV-2 has underlined the critical need for new antiviral medicines. Many of the discovered inhibitors have off-target effects or toxicity issues, but no single lead chemical has been found as a powerful SARS-CoV-2 inhibitor. Small-molecule metabolites from human blood, for example, have been demonstrated to exhibit biological action, such as anti-inflammatory or antiviral properties, but have not been reported as pharmacophore-based drug discovery models.
Aims: To evaluate the feasibility of employing pharmacophore models of small-molecule metabolites taken from human blood as a lead discovery method for SARS-CoV-2 inhibitors.
Methods: A total of six small-molecule metabolites from human blood were utilized to construct a pharmacophore model, which was then used to simulate the interaction’s stability for the top two-rank ligands with the best interactions using molecular docking and molecular dynamics.
Results: The area under the curve value of the pharmacophore model created using the best pairwise alignments approach was 0.576, indicating that it is suitably validated as a model. The pharmacophore model was utilized for virtual screening, followed by molecular docking, yielding 75 hits. An investigation of the molecular dynamics of two top-rank hits (ZINC000085567845 and ZINC000085567870) revealed a stable interaction with the SARS-CoV-2 spike protein.
Conclusions: Finally, the pharmacophore model developed was capable of discovering lead compounds with the potential as SARS-CoV-2 spike protein inhibitors. |
| first_indexed | 2024-03-12T00:01:25Z |
| format | Article |
| id | doaj.art-beab6fcc4fe9447aaa108c4b3055848e |
| institution | Directory Open Access Journal |
| issn | 0719-4250 |
| language | English |
| last_indexed | 2024-03-12T00:01:25Z |
| publishDate | 2023-09-01 |
| publisher | GarVal Editorial Ltda. |
| record_format | Article |
| series | Journal of Pharmacy & Pharmacognosy Research |
| spelling | doaj.art-beab6fcc4fe9447aaa108c4b3055848e2023-09-17T18:57:01ZengGarVal Editorial Ltda.Journal of Pharmacy & Pharmacognosy Research0719-42502023-09-0111581082210.56499/jppres23.1688_11.5.810Lead compound discovery using pharmacophore-based models of small-molecule metabolites from human blood as inhibitor cellular entry of SARS-CoV-2Ellin Febrina0Aiyi Asnawi1Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Sumedang, West Java, 45363, Indonesia.Faculty of Pharmacy, Universitas Bhakti Kencana, Jl. Soekarno Hatta No.754, Bandung, West Java, 40617, Indonesia.Context: The development of emerging viral diseases like SARS-CoV-2 has underlined the critical need for new antiviral medicines. Many of the discovered inhibitors have off-target effects or toxicity issues, but no single lead chemical has been found as a powerful SARS-CoV-2 inhibitor. Small-molecule metabolites from human blood, for example, have been demonstrated to exhibit biological action, such as anti-inflammatory or antiviral properties, but have not been reported as pharmacophore-based drug discovery models. Aims: To evaluate the feasibility of employing pharmacophore models of small-molecule metabolites taken from human blood as a lead discovery method for SARS-CoV-2 inhibitors. Methods: A total of six small-molecule metabolites from human blood were utilized to construct a pharmacophore model, which was then used to simulate the interaction’s stability for the top two-rank ligands with the best interactions using molecular docking and molecular dynamics. Results: The area under the curve value of the pharmacophore model created using the best pairwise alignments approach was 0.576, indicating that it is suitably validated as a model. The pharmacophore model was utilized for virtual screening, followed by molecular docking, yielding 75 hits. An investigation of the molecular dynamics of two top-rank hits (ZINC000085567845 and ZINC000085567870) revealed a stable interaction with the SARS-CoV-2 spike protein. Conclusions: Finally, the pharmacophore model developed was capable of discovering lead compounds with the potential as SARS-CoV-2 spike protein inhibitors.https://jppres.com/jppres/pdf/vol11/jppres23.1688_11.5.810.pdfantiviralmolecular dockingmolecular dynamicssars-cov-2screeningcovid-19 |
| spellingShingle | Ellin Febrina Aiyi Asnawi Lead compound discovery using pharmacophore-based models of small-molecule metabolites from human blood as inhibitor cellular entry of SARS-CoV-2 Journal of Pharmacy & Pharmacognosy Research antiviral molecular docking molecular dynamics sars-cov-2 screening covid-19 |
| title | Lead compound discovery using pharmacophore-based models of small-molecule metabolites from human blood as inhibitor cellular entry of SARS-CoV-2 |
| title_full | Lead compound discovery using pharmacophore-based models of small-molecule metabolites from human blood as inhibitor cellular entry of SARS-CoV-2 |
| title_fullStr | Lead compound discovery using pharmacophore-based models of small-molecule metabolites from human blood as inhibitor cellular entry of SARS-CoV-2 |
| title_full_unstemmed | Lead compound discovery using pharmacophore-based models of small-molecule metabolites from human blood as inhibitor cellular entry of SARS-CoV-2 |
| title_short | Lead compound discovery using pharmacophore-based models of small-molecule metabolites from human blood as inhibitor cellular entry of SARS-CoV-2 |
| title_sort | lead compound discovery using pharmacophore based models of small molecule metabolites from human blood as inhibitor cellular entry of sars cov 2 |
| topic | antiviral molecular docking molecular dynamics sars-cov-2 screening covid-19 |
| url | https://jppres.com/jppres/pdf/vol11/jppres23.1688_11.5.810.pdf |
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