Computer-Aided Discovery of Compounds With Anti-Schistosomal Potential
Schistosomiasis, which causes over 200 000 deaths annually, has since the 1970s been controlled by praziquintel. The reliance on a single drug to combat schistosomiasis, and reports of laboratory resistance to the drug, has created an urgent need in the scientific community to develop new chemothera...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2024-11-01
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| Series: | Biomedical Engineering and Computational Biology |
| Online Access: | https://doi.org/10.1177/11795972241294112 |
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| _version_ | 1846170992494247936 |
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| author | Ryman Shoko Allen Mazadza |
| author_facet | Ryman Shoko Allen Mazadza |
| author_sort | Ryman Shoko |
| collection | DOAJ |
| description | Schistosomiasis, which causes over 200 000 deaths annually, has since the 1970s been controlled by praziquintel. The reliance on a single drug to combat schistosomiasis, and reports of laboratory resistance to the drug, has created an urgent need in the scientific community to develop new chemotherapies to complement or supplement praziquantel. Medicinal plants are a potential reservoir of compounds with schistosomicidal activity. In the current study, we carried out computer-aided screening of Abrus precatorius compounds to discover compounds with potential to inhibit Schistosoma mansoni purine nucleoside phosphorylase ( Sm PNP). Thus, 99 compounds retrieved from Lotus Natural Compounds Database were docked into the active site of Sm PNP. The top-ranked compounds were subjected to Lipinski’s druglikeness and toxicity risk predictions. Three lead compounds, abrusogenin, cirsimaritin and hispidulin, were identified as having high binding affinities, favourable interactions with Sm PNP active site residues and good toxicity risk prediction results. Molecular dynamics (MD) simulations were used to assess the stability of the interactions of these lead compounds with Sm PNP. Collectively, analyses of the MD trajectories confirms that the lead compounds bound and interacted stably with active site residues of Sm PNP. We conclude that abrusogenin, cirsimaritin and hispidulin could serve as hit compounds for the development of new antischistosomal drugs, based on plant-derived natural products. However, experimental studies are required to further evaluate the potentials of these compounds as possible therapeutics against schistosomiasis. |
| format | Article |
| id | doaj-art-b32c7f6c984e4de0b3ba6805b1893776 |
| institution | Kabale University |
| issn | 1179-5972 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Biomedical Engineering and Computational Biology |
| spelling | doaj-art-b32c7f6c984e4de0b3ba6805b18937762024-11-11T09:03:19ZengSAGE PublishingBiomedical Engineering and Computational Biology1179-59722024-11-011510.1177/11795972241294112Computer-Aided Discovery of Compounds With Anti-Schistosomal PotentialRyman ShokoAllen MazadzaSchistosomiasis, which causes over 200 000 deaths annually, has since the 1970s been controlled by praziquintel. The reliance on a single drug to combat schistosomiasis, and reports of laboratory resistance to the drug, has created an urgent need in the scientific community to develop new chemotherapies to complement or supplement praziquantel. Medicinal plants are a potential reservoir of compounds with schistosomicidal activity. In the current study, we carried out computer-aided screening of Abrus precatorius compounds to discover compounds with potential to inhibit Schistosoma mansoni purine nucleoside phosphorylase ( Sm PNP). Thus, 99 compounds retrieved from Lotus Natural Compounds Database were docked into the active site of Sm PNP. The top-ranked compounds were subjected to Lipinski’s druglikeness and toxicity risk predictions. Three lead compounds, abrusogenin, cirsimaritin and hispidulin, were identified as having high binding affinities, favourable interactions with Sm PNP active site residues and good toxicity risk prediction results. Molecular dynamics (MD) simulations were used to assess the stability of the interactions of these lead compounds with Sm PNP. Collectively, analyses of the MD trajectories confirms that the lead compounds bound and interacted stably with active site residues of Sm PNP. We conclude that abrusogenin, cirsimaritin and hispidulin could serve as hit compounds for the development of new antischistosomal drugs, based on plant-derived natural products. However, experimental studies are required to further evaluate the potentials of these compounds as possible therapeutics against schistosomiasis.https://doi.org/10.1177/11795972241294112 |
| spellingShingle | Ryman Shoko Allen Mazadza Computer-Aided Discovery of Compounds With Anti-Schistosomal Potential Biomedical Engineering and Computational Biology |
| title | Computer-Aided Discovery of Compounds With Anti-Schistosomal Potential |
| title_full | Computer-Aided Discovery of Compounds With Anti-Schistosomal Potential |
| title_fullStr | Computer-Aided Discovery of Compounds With Anti-Schistosomal Potential |
| title_full_unstemmed | Computer-Aided Discovery of Compounds With Anti-Schistosomal Potential |
| title_short | Computer-Aided Discovery of Compounds With Anti-Schistosomal Potential |
| title_sort | computer aided discovery of compounds with anti schistosomal potential |
| url | https://doi.org/10.1177/11795972241294112 |
| work_keys_str_mv | AT rymanshoko computeraideddiscoveryofcompoundswithantischistosomalpotential AT allenmazadza computeraideddiscoveryofcompoundswithantischistosomalpotential |