Pharmacophore-based virtual screening and in-silico study of natural products as potential DENV-2 RdRp inhibitors
Dengue fever is a significant public health concern throughout the world, causing an estimated 500,000 hospitalizations and 20,000 deaths each year, despite the lack of effective therapies. The DENV-2 RdRp has been identified as a potential target for the development of new and effective dengue ther...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English English |
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Taylor & Francis
2023
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| Online Access: | http://umpir.ump.edu.my/id/eprint/37892/1/Pharmacophore-based%20virtual%20screening%20and%20in-silico%20study.pdf http://umpir.ump.edu.my/id/eprint/37892/13/Pharmacophore-based%20virtual%20screening%20and%20in-silico%20study%20of%20natural%20products%20as%20potential%20DENV-2%20RdRp%20inhibitors.pdf |
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| author | Miah, Roney A. K. M., Moyeenul Huq Abdul Rashid, Issahaku Mahmoud E. S., Soliman Md. Sanower, Hossain Abu Hasnat, Mustafa Md. Alimul, Islam Amit, Dubey Aisha, Tufail Mohd Fadhlizil Fasihi, Mohd Aluwi Saiful Nizam, Tajuddin |
| author_facet | Miah, Roney A. K. M., Moyeenul Huq Abdul Rashid, Issahaku Mahmoud E. S., Soliman Md. Sanower, Hossain Abu Hasnat, Mustafa Md. Alimul, Islam Amit, Dubey Aisha, Tufail Mohd Fadhlizil Fasihi, Mohd Aluwi Saiful Nizam, Tajuddin |
| author_sort | Miah, Roney |
| collection | UMP |
| description | Dengue fever is a significant public health concern throughout the world, causing an estimated 500,000 hospitalizations and 20,000 deaths each year, despite the lack of effective therapies. The DENV-2 RdRp has been identified as a potential target for the development of new and effective dengue therapies. This research’s primary objective was to discover an anti-DENV inhibitor using in silico ligand- and structure-based approaches. To begin, a ligand-based pharmacophore model was developed, and 130 distinct natural products (NPs) were screened. Docking of the pharmacophore-matched compounds were performed to the active site of DENV-2 RdRp protease . Eleven compounds were identified as potential DENV-2 RdRp inhibitors based on docking energy and binding interactions. ADMET and drug-likeness were done to predict their pharmacologic, pharmacokinetic, and drug-likeproperties . Compounds ranked highest in terms of pharmacokinetics and drug-like appearances were then subjected to additional toxicity testing to determine the leading compound. Additionally, MD simulation of the lead compound was performed to confirm the docked complex’s stability and the binding site determined by docking. As a result, the lead compound (compound-108) demonstrated an excellent match to the pharmacophore, a strong binding contact and affinity for the RdRp enzyme, favourable pharmacokinetics, and drug-like characteristics. In summary, the lead compound identified in this study could be a possible DENV-2 RdRp inhibitor that may be further studied on in vitro and in vivo models to develop as a drug candidate. |
| first_indexed | 2024-03-06T13:07:09Z |
| format | Article |
| id | UMPir37892 |
| institution | Universiti Malaysia Pahang |
| language | English English |
| last_indexed | 2024-03-06T13:07:09Z |
| publishDate | 2023 |
| publisher | Taylor & Francis |
| record_format | dspace |
| spelling | UMPir378922023-11-22T03:38:34Z http://umpir.ump.edu.my/id/eprint/37892/ Pharmacophore-based virtual screening and in-silico study of natural products as potential DENV-2 RdRp inhibitors Miah, Roney A. K. M., Moyeenul Huq Abdul Rashid, Issahaku Mahmoud E. S., Soliman Md. Sanower, Hossain Abu Hasnat, Mustafa Md. Alimul, Islam Amit, Dubey Aisha, Tufail Mohd Fadhlizil Fasihi, Mohd Aluwi Saiful Nizam, Tajuddin Q Science (General) R Medicine (General) T Technology (General) Dengue fever is a significant public health concern throughout the world, causing an estimated 500,000 hospitalizations and 20,000 deaths each year, despite the lack of effective therapies. The DENV-2 RdRp has been identified as a potential target for the development of new and effective dengue therapies. This research’s primary objective was to discover an anti-DENV inhibitor using in silico ligand- and structure-based approaches. To begin, a ligand-based pharmacophore model was developed, and 130 distinct natural products (NPs) were screened. Docking of the pharmacophore-matched compounds were performed to the active site of DENV-2 RdRp protease . Eleven compounds were identified as potential DENV-2 RdRp inhibitors based on docking energy and binding interactions. ADMET and drug-likeness were done to predict their pharmacologic, pharmacokinetic, and drug-likeproperties . Compounds ranked highest in terms of pharmacokinetics and drug-like appearances were then subjected to additional toxicity testing to determine the leading compound. Additionally, MD simulation of the lead compound was performed to confirm the docked complex’s stability and the binding site determined by docking. As a result, the lead compound (compound-108) demonstrated an excellent match to the pharmacophore, a strong binding contact and affinity for the RdRp enzyme, favourable pharmacokinetics, and drug-like characteristics. In summary, the lead compound identified in this study could be a possible DENV-2 RdRp inhibitor that may be further studied on in vitro and in vivo models to develop as a drug candidate. Taylor & Francis 2023 Article PeerReviewed pdf en http://umpir.ump.edu.my/id/eprint/37892/1/Pharmacophore-based%20virtual%20screening%20and%20in-silico%20study.pdf pdf en http://umpir.ump.edu.my/id/eprint/37892/13/Pharmacophore-based%20virtual%20screening%20and%20in-silico%20study%20of%20natural%20products%20as%20potential%20DENV-2%20RdRp%20inhibitors.pdf Miah, Roney and A. K. M., Moyeenul Huq and Abdul Rashid, Issahaku and Mahmoud E. S., Soliman and Md. Sanower, Hossain and Abu Hasnat, Mustafa and Md. Alimul, Islam and Amit, Dubey and Aisha, Tufail and Mohd Fadhlizil Fasihi, Mohd Aluwi and Saiful Nizam, Tajuddin (2023) Pharmacophore-based virtual screening and in-silico study of natural products as potential DENV-2 RdRp inhibitors. Journal of Biomolecular Structure and Dynamics, 41 (21). pp. 12186-12203. ISSN 0739-1102. (Published) https://doi.org/10.1080/07391102.2023.2166123 https://doi.org/10.1080/07391102.2023.2166123 |
| spellingShingle | Q Science (General) R Medicine (General) T Technology (General) Miah, Roney A. K. M., Moyeenul Huq Abdul Rashid, Issahaku Mahmoud E. S., Soliman Md. Sanower, Hossain Abu Hasnat, Mustafa Md. Alimul, Islam Amit, Dubey Aisha, Tufail Mohd Fadhlizil Fasihi, Mohd Aluwi Saiful Nizam, Tajuddin Pharmacophore-based virtual screening and in-silico study of natural products as potential DENV-2 RdRp inhibitors |
| title | Pharmacophore-based virtual screening and in-silico study of natural products as potential DENV-2 RdRp inhibitors |
| title_full | Pharmacophore-based virtual screening and in-silico study of natural products as potential DENV-2 RdRp inhibitors |
| title_fullStr | Pharmacophore-based virtual screening and in-silico study of natural products as potential DENV-2 RdRp inhibitors |
| title_full_unstemmed | Pharmacophore-based virtual screening and in-silico study of natural products as potential DENV-2 RdRp inhibitors |
| title_short | Pharmacophore-based virtual screening and in-silico study of natural products as potential DENV-2 RdRp inhibitors |
| title_sort | pharmacophore based virtual screening and in silico study of natural products as potential denv 2 rdrp inhibitors |
| topic | Q Science (General) R Medicine (General) T Technology (General) |
| url | http://umpir.ump.edu.my/id/eprint/37892/1/Pharmacophore-based%20virtual%20screening%20and%20in-silico%20study.pdf http://umpir.ump.edu.my/id/eprint/37892/13/Pharmacophore-based%20virtual%20screening%20and%20in-silico%20study%20of%20natural%20products%20as%20potential%20DENV-2%20RdRp%20inhibitors.pdf |
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