Azhar Iqbal , Hassan Bin Waseem , Faisal Ali , Soukayna Baammi , Hira Faheem , Gamal A. Shazly , Hiba-Allah Nafidi , Muhammad Sajid , Muhammad Saleem Khan , Hafiza Nisha Akram , Moawaz Aziz , Noshaba Dilbar , Saad Qamar , Asif Mir , Mohammed Bourhia , Sheikh Arslan Sehgal
{"title":"通过硅学鉴定和虚拟筛选发现针对 CMT2A 的强效治疗植物化学物质","authors":"Azhar Iqbal , Hassan Bin Waseem , Faisal Ali , Soukayna Baammi , Hira Faheem , Gamal A. Shazly , Hiba-Allah Nafidi , Muhammad Sajid , Muhammad Saleem Khan , Hafiza Nisha Akram , Moawaz Aziz , Noshaba Dilbar , Saad Qamar , Asif Mir , Mohammed Bourhia , Sheikh Arslan Sehgal","doi":"10.1016/j.jics.2024.101403","DOIUrl":null,"url":null,"abstract":"<div><div>Charcot-Marie-Tooth (CMT2A) neuropathies are a set of monogenic diseases that affect the peripheral nervous system. The pathogenesis of CMT2A, a disease caused by genetic mutations, is linked to impaired mitochondrial dynamics and axonal biology. Therapeutic options are still limited, with only a few drugs and other authorized or underdeveloped approaches. A ligand-based virtual screening methodology was used to identify the potential MFN promoters. The natural compound subset of the ZINC database (n = 559600) was obtained and filtered using a ligand-based virtual screening technique. The top 200 compounds were identified to have more than four features that matched the target compound. Pyrx software was used to analyze the molecular docking. Based on the number and type of important binding interactions and docking results, we selected top-20 compounds with the best binding affinities for the targeted protein. 3D-QSAR analyses were performed on potential ligands identified through molecular docking analyses to predict biological activity. The pEC50 and docking scores were used to identify the potential drugs. The ADMET analysis was used to assess the kinetic characteristics of the top two drugs. According to molecular dynamics simulation, the top compound ZINC000005313168 showed high conformational stability. Based on docking results and MD findings, the best in silico hits among the compounds investigated was ZINC000005313168. These findings suggest that the compound ZINC000005313168 could be used to treat CMT2A disease. Further <em>in vivo</em> and <em>in vitro</em> studies are required to consider the present analyses.</div></div>","PeriodicalId":17276,"journal":{"name":"Journal of the Indian Chemical Society","volume":"101 11","pages":"Article 101403"},"PeriodicalIF":3.2000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"In silico identification and virtual screening to discover potent therapeutic phytochemicals against CMT2A\",\"authors\":\"Azhar Iqbal , Hassan Bin Waseem , Faisal Ali , Soukayna Baammi , Hira Faheem , Gamal A. Shazly , Hiba-Allah Nafidi , Muhammad Sajid , Muhammad Saleem Khan , Hafiza Nisha Akram , Moawaz Aziz , Noshaba Dilbar , Saad Qamar , Asif Mir , Mohammed Bourhia , Sheikh Arslan Sehgal\",\"doi\":\"10.1016/j.jics.2024.101403\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Charcot-Marie-Tooth (CMT2A) neuropathies are a set of monogenic diseases that affect the peripheral nervous system. The pathogenesis of CMT2A, a disease caused by genetic mutations, is linked to impaired mitochondrial dynamics and axonal biology. Therapeutic options are still limited, with only a few drugs and other authorized or underdeveloped approaches. A ligand-based virtual screening methodology was used to identify the potential MFN promoters. The natural compound subset of the ZINC database (n = 559600) was obtained and filtered using a ligand-based virtual screening technique. The top 200 compounds were identified to have more than four features that matched the target compound. Pyrx software was used to analyze the molecular docking. Based on the number and type of important binding interactions and docking results, we selected top-20 compounds with the best binding affinities for the targeted protein. 3D-QSAR analyses were performed on potential ligands identified through molecular docking analyses to predict biological activity. The pEC50 and docking scores were used to identify the potential drugs. The ADMET analysis was used to assess the kinetic characteristics of the top two drugs. According to molecular dynamics simulation, the top compound ZINC000005313168 showed high conformational stability. Based on docking results and MD findings, the best in silico hits among the compounds investigated was ZINC000005313168. These findings suggest that the compound ZINC000005313168 could be used to treat CMT2A disease. Further <em>in vivo</em> and <em>in vitro</em> studies are required to consider the present analyses.</div></div>\",\"PeriodicalId\":17276,\"journal\":{\"name\":\"Journal of the Indian Chemical Society\",\"volume\":\"101 11\",\"pages\":\"Article 101403\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-10-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of the Indian Chemical Society\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0019452224002838\",\"RegionNum\":4,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the Indian Chemical Society","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0019452224002838","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
In silico identification and virtual screening to discover potent therapeutic phytochemicals against CMT2A
Charcot-Marie-Tooth (CMT2A) neuropathies are a set of monogenic diseases that affect the peripheral nervous system. The pathogenesis of CMT2A, a disease caused by genetic mutations, is linked to impaired mitochondrial dynamics and axonal biology. Therapeutic options are still limited, with only a few drugs and other authorized or underdeveloped approaches. A ligand-based virtual screening methodology was used to identify the potential MFN promoters. The natural compound subset of the ZINC database (n = 559600) was obtained and filtered using a ligand-based virtual screening technique. The top 200 compounds were identified to have more than four features that matched the target compound. Pyrx software was used to analyze the molecular docking. Based on the number and type of important binding interactions and docking results, we selected top-20 compounds with the best binding affinities for the targeted protein. 3D-QSAR analyses were performed on potential ligands identified through molecular docking analyses to predict biological activity. The pEC50 and docking scores were used to identify the potential drugs. The ADMET analysis was used to assess the kinetic characteristics of the top two drugs. According to molecular dynamics simulation, the top compound ZINC000005313168 showed high conformational stability. Based on docking results and MD findings, the best in silico hits among the compounds investigated was ZINC000005313168. These findings suggest that the compound ZINC000005313168 could be used to treat CMT2A disease. Further in vivo and in vitro studies are required to consider the present analyses.
期刊介绍:
The Journal of the Indian Chemical Society publishes original, fundamental, theorical, experimental research work of highest quality in all areas of chemistry, biochemistry, medicinal chemistry, electrochemistry, agrochemistry, chemical engineering and technology, food chemistry, environmental chemistry, etc.