Reprofiling analysis of FDA approved drugs with upregulated differential expression genes found in hypertension
Background: Hypertension is one of the most devastating human health problems with a higher incidence of both mortality and morbidity. The prevalence of this disease is more pronounced in underdeveloped countries as compared to developed countries. Drug discovery and development is a complex, time-c...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Informatics in Medicine Unlocked |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352914822000478 |
| _version_ | 1819079060230242304 |
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| author | Fawad Ali He Liu Fang Fawad Ali Shah Syed Aun Muhammad Arifullah Khan Shupeng Li |
| author_facet | Fawad Ali He Liu Fang Fawad Ali Shah Syed Aun Muhammad Arifullah Khan Shupeng Li |
| author_sort | Fawad Ali |
| collection | DOAJ |
| description | Background: Hypertension is one of the most devastating human health problems with a higher incidence of both mortality and morbidity. The prevalence of this disease is more pronounced in underdeveloped countries as compared to developed countries. Drug discovery and development is a complex, time-consuming process, associated with increased failure risk. Therefore, the drug development process declined to the lowest in the history of the pharmaceutical industry during the past several years Therefore, drug reprofiling could be a lucrative approach for the novice in the field of new drug discovery and development. Methods: In this study in silico drug repurposing method was used to find the best drug candidate for hypertension using the differential expression genes (DEGs) approach. We performed a molecular docking analysis of 2500 drugs from FDA-approved databases against the selected DEGs for lead identification. Furthermore, molecular docking (MD) simulation was performed to analyze the stability of the interacting complexes. Results: We screened FDA-approved drugs against the four selected overexpressed DEGs using the molecular operating environment (MOE). These DEGs were adrenomedullin (ADM), ubiquitin-specific peptidase-8 (USP-8), angiopoietin-like-4 (ANGPTL-4), and endothelin-1 (EDN1). The three top-ranked drug candidates against each target protein were shortlisted. Moreover, these twelve complexes after docking were validated by the molecular dynamics (MD) simulation for 100 ns with the active sites of the target. Conclusions: Based on the high binding affinity and stability of the drug complexes, we demonstrated here that these molecules could be investigated further as a potential drug candidate for hypertension. |
| first_indexed | 2024-12-21T19:22:59Z |
| format | Article |
| id | doaj.art-77f6a2d012e848569116ca10e3c96e1a |
| institution | Directory Open Access Journal |
| issn | 2352-9148 |
| language | English |
| last_indexed | 2024-12-21T19:22:59Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Informatics in Medicine Unlocked |
| spelling | doaj.art-77f6a2d012e848569116ca10e3c96e1a2022-12-21T18:52:54ZengElsevierInformatics in Medicine Unlocked2352-91482022-01-0129100895Reprofiling analysis of FDA approved drugs with upregulated differential expression genes found in hypertensionFawad Ali0He Liu Fang1Fawad Ali Shah2Syed Aun Muhammad3Arifullah Khan4Shupeng Li5Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, 44000, Pakistan; Department of Pharmacy Kohat University of Science and Technology, Kohat, 26000, Pakistan; Corresponding author. State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Peking University, Shenzhen, China.Department of Neonatology, Affiliated Longhua People's Hospital, Southern Medical University Shenzen, 518109, ChinaRiphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, 44000, PakistanInstitute of Molecular Biology and Biotechnology Bahauddin Zakariya University, Multan, 60800, PakistanRiphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, 44000, PakistanState Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Peking University, Shenzhen, China; Corresponding author. Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, 44000, Pakistan.Background: Hypertension is one of the most devastating human health problems with a higher incidence of both mortality and morbidity. The prevalence of this disease is more pronounced in underdeveloped countries as compared to developed countries. Drug discovery and development is a complex, time-consuming process, associated with increased failure risk. Therefore, the drug development process declined to the lowest in the history of the pharmaceutical industry during the past several years Therefore, drug reprofiling could be a lucrative approach for the novice in the field of new drug discovery and development. Methods: In this study in silico drug repurposing method was used to find the best drug candidate for hypertension using the differential expression genes (DEGs) approach. We performed a molecular docking analysis of 2500 drugs from FDA-approved databases against the selected DEGs for lead identification. Furthermore, molecular docking (MD) simulation was performed to analyze the stability of the interacting complexes. Results: We screened FDA-approved drugs against the four selected overexpressed DEGs using the molecular operating environment (MOE). These DEGs were adrenomedullin (ADM), ubiquitin-specific peptidase-8 (USP-8), angiopoietin-like-4 (ANGPTL-4), and endothelin-1 (EDN1). The three top-ranked drug candidates against each target protein were shortlisted. Moreover, these twelve complexes after docking were validated by the molecular dynamics (MD) simulation for 100 ns with the active sites of the target. Conclusions: Based on the high binding affinity and stability of the drug complexes, we demonstrated here that these molecules could be investigated further as a potential drug candidate for hypertension.http://www.sciencedirect.com/science/article/pii/S2352914822000478Reprofiling hypertensionDifferential gene expressionSimulations |
| spellingShingle | Fawad Ali He Liu Fang Fawad Ali Shah Syed Aun Muhammad Arifullah Khan Shupeng Li Reprofiling analysis of FDA approved drugs with upregulated differential expression genes found in hypertension Informatics in Medicine Unlocked Reprofiling hypertension Differential gene expression Simulations |
| title | Reprofiling analysis of FDA approved drugs with upregulated differential expression genes found in hypertension |
| title_full | Reprofiling analysis of FDA approved drugs with upregulated differential expression genes found in hypertension |
| title_fullStr | Reprofiling analysis of FDA approved drugs with upregulated differential expression genes found in hypertension |
| title_full_unstemmed | Reprofiling analysis of FDA approved drugs with upregulated differential expression genes found in hypertension |
| title_short | Reprofiling analysis of FDA approved drugs with upregulated differential expression genes found in hypertension |
| title_sort | reprofiling analysis of fda approved drugs with upregulated differential expression genes found in hypertension |
| topic | Reprofiling hypertension Differential gene expression Simulations |
| url | http://www.sciencedirect.com/science/article/pii/S2352914822000478 |
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