{"title":"从 Euphorbia neriifolia (Dudsor) 提取物中鉴定作为 SARS-CoV-2 ACE2-RBDS1 受体复合物潜在抑制剂的主要化合物:分子对接 ADMET 分析和 MD 模拟研究的启示。","authors":"Md Nur Islam, Md Enayet Ali Pramanik, Md Arju Hossain, Md Hasanur Rahman, Md Sahadot Hossen, Md Ashraful Islam, M Morsed Zaman Miah, Istiak Ahmed, Azm Mostaque Hossain, Md Jawadul Haque, Akm Monoarul Islam, Md Nowshad Ali, Rukhshana Akhter Jahan, Md Enamul Haque, Md Munzur Rahman, Md Sharif Hasan, Mohammad Motiur Rahman, Md Mamun Kabir, Prabir Mohan Basak, Md Abdul Mumit Sarkar, Md Shafiqul Islam, Md Rashedur Rahman, Akm Azad-Ud-Doula Prodhan, Ashik Mosaddik, Humayra Haque, Fahmida Fahmin, Haimanti Shukla Das, Md Manzurul Islam, Chandrima Emtia, Md Royhan Gofur, Aiping Liang, Sheikh Mohammad Fazle Akbar","doi":"10.5005/jp-journals-10018-1414","DOIUrl":null,"url":null,"abstract":"<p><p>Coronavirus disease-19 (COVID-19) are deadly and infectious disease that impacts individuals in a variety of ways. Scientists have stepped up their attempts to find an antiviral drug that targets the spike protein (S) of Angiotensin converting enzyme 2 (ACE2) (receptor protein) as a viable therapeutic target for coronavirus. The most recent study examines the potential antagonistic effects of 17 phytochemicals present in the plant extraction of <i>Euphorbia neriifolia</i> on the anti-SARS-CoV-2 ACE2 protein. Computational techniques like molecular docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET) investigations, and molecular dynamics (MD) simulation analysis were used to investigate the actions of these phytochemicals. The results of molecular docking studies showed that the control ligand (2-acetamido-2-deoxy-β-D-glucopyranose) had a binding potential of -6.2 kcal/mol, but the binding potentials of delphin, β-amyrin, and tulipanin are greater at -10.4, 10.0, and -9.6 kcal/mol. To verify their drug-likeness, the discovered hits were put via Lipinski filters and ADMET analysis. According to MD simulations of the complex run for 100 numbers, delphin binds to the SARS-CoV-2 ACE2 receptor's active region with good stability. In root-mean-square deviation (RMSD) and root mean square fluctuation (RMSF) calculations, delphinan, β-amyrin, and tulipanin showed reduced variance with the receptor binding domain subunit 1(RBD S1) ACE2 protein complex. The solvent accessible surface area (SASA), radius of gyration (Rg), molecular surface area (MolSA), and polar surface area (PSA) validation results for these three compounds were likewise encouraging. The convenient binding energies across the 100 numbers binding period were discovered by using molecular mechanics of generalized born and surface (MM/GBSA) to estimate the ligand-binding free energies to the protein receptor. All things considered, the information points to a greater likelihood of chemicals found in <i>Euphorbia neriifolia</i> binding to the SARS-CoV-2 ACE2 active site. To determine these lead compounds' anti-SARS-CoV-2 potential, in vitro and <i>in vivo</i> studies should be conducted.</p><p><strong>How to cite this article: </strong>Islam MN, Pramanik MEA, Hossain MA, <i>et al</i>. Identification of Leading Compounds from <i>Euphorbia Neriifolia</i> (Dudsor) Extracts as a Potential Inhibitor of SARS-CoV-2 ACE2-RBDS1 Receptor Complex: An Insight from Molecular Docking ADMET Profiling and MD-simulation Studies. Euroasian J Hepato-Gastroenterol 2023;13(2):89-107.</p>","PeriodicalId":516317,"journal":{"name":"Euroasian journal of hepato-gastroenterology","volume":"13 2","pages":"89-107"},"PeriodicalIF":0.0000,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10785135/pdf/","citationCount":"0","resultStr":"{\"title\":\"Identification of Leading Compounds from <i>Euphorbia neriifolia</i> (Dudsor) Extracts as a Potential Inhibitor of SARS-CoV-2 ACE2-RBDS1 Receptor Complex: An Insight from Molecular Docking ADMET Profiling and MD-simulation Studies.\",\"authors\":\"Md Nur Islam, Md Enayet Ali Pramanik, Md Arju Hossain, Md Hasanur Rahman, Md Sahadot Hossen, Md Ashraful Islam, M Morsed Zaman Miah, Istiak Ahmed, Azm Mostaque Hossain, Md Jawadul Haque, Akm Monoarul Islam, Md Nowshad Ali, Rukhshana Akhter Jahan, Md Enamul Haque, Md Munzur Rahman, Md Sharif Hasan, Mohammad Motiur Rahman, Md Mamun Kabir, Prabir Mohan Basak, Md Abdul Mumit Sarkar, Md Shafiqul Islam, Md Rashedur Rahman, Akm Azad-Ud-Doula Prodhan, Ashik Mosaddik, Humayra Haque, Fahmida Fahmin, Haimanti Shukla Das, Md Manzurul Islam, Chandrima Emtia, Md Royhan Gofur, Aiping Liang, Sheikh Mohammad Fazle Akbar\",\"doi\":\"10.5005/jp-journals-10018-1414\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Coronavirus disease-19 (COVID-19) are deadly and infectious disease that impacts individuals in a variety of ways. Scientists have stepped up their attempts to find an antiviral drug that targets the spike protein (S) of Angiotensin converting enzyme 2 (ACE2) (receptor protein) as a viable therapeutic target for coronavirus. The most recent study examines the potential antagonistic effects of 17 phytochemicals present in the plant extraction of <i>Euphorbia neriifolia</i> on the anti-SARS-CoV-2 ACE2 protein. Computational techniques like molecular docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET) investigations, and molecular dynamics (MD) simulation analysis were used to investigate the actions of these phytochemicals. The results of molecular docking studies showed that the control ligand (2-acetamido-2-deoxy-β-D-glucopyranose) had a binding potential of -6.2 kcal/mol, but the binding potentials of delphin, β-amyrin, and tulipanin are greater at -10.4, 10.0, and -9.6 kcal/mol. To verify their drug-likeness, the discovered hits were put via Lipinski filters and ADMET analysis. According to MD simulations of the complex run for 100 numbers, delphin binds to the SARS-CoV-2 ACE2 receptor's active region with good stability. In root-mean-square deviation (RMSD) and root mean square fluctuation (RMSF) calculations, delphinan, β-amyrin, and tulipanin showed reduced variance with the receptor binding domain subunit 1(RBD S1) ACE2 protein complex. The solvent accessible surface area (SASA), radius of gyration (Rg), molecular surface area (MolSA), and polar surface area (PSA) validation results for these three compounds were likewise encouraging. The convenient binding energies across the 100 numbers binding period were discovered by using molecular mechanics of generalized born and surface (MM/GBSA) to estimate the ligand-binding free energies to the protein receptor. All things considered, the information points to a greater likelihood of chemicals found in <i>Euphorbia neriifolia</i> binding to the SARS-CoV-2 ACE2 active site. To determine these lead compounds' anti-SARS-CoV-2 potential, in vitro and <i>in vivo</i> studies should be conducted.</p><p><strong>How to cite this article: </strong>Islam MN, Pramanik MEA, Hossain MA, <i>et al</i>. Identification of Leading Compounds from <i>Euphorbia Neriifolia</i> (Dudsor) Extracts as a Potential Inhibitor of SARS-CoV-2 ACE2-RBDS1 Receptor Complex: An Insight from Molecular Docking ADMET Profiling and MD-simulation Studies. Euroasian J Hepato-Gastroenterol 2023;13(2):89-107.</p>\",\"PeriodicalId\":516317,\"journal\":{\"name\":\"Euroasian journal of hepato-gastroenterology\",\"volume\":\"13 2\",\"pages\":\"89-107\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10785135/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Euroasian journal of hepato-gastroenterology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.5005/jp-journals-10018-1414\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Euroasian journal of hepato-gastroenterology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.5005/jp-journals-10018-1414","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
冠状病毒病-19(COVID-19)是一种致命的传染性疾病,会以各种方式对人体造成影响。科学家们一直在努力寻找一种以血管紧张素转换酶 2(ACE2)的尖峰蛋白(S)(受体蛋白)为靶点的抗病毒药物,作为冠状病毒的可行治疗靶点。最新的研究探讨了从 Euphorbia neriifolia 植物提取物中提取的 17 种植物化学物质对抗 SARS-CoV-2 ACE2 蛋白的潜在拮抗作用。研究人员采用了分子对接、吸收、分布、代谢、排泄和毒性(ADMET)调查以及分子动力学(MD)模拟分析等计算技术来研究这些植物化学物质的作用。分子对接研究结果表明,对照配体(2-乙酰氨基-2-脱氧-β-D-吡喃葡萄糖)的结合位势为-6.2 kcal/mol,而脱氢素、β-amyrin和郁金香苷的结合位势较大,分别为-10.4、10.0和-9.6 kcal/mol。为了验证这些化合物的药物相似性,我们对发现的化合物进行了利宾斯基过滤和 ADMET 分析。根据对复合物运行 100 次的 MD 模拟,delphin 与 SARS-CoV-2 ACE2 受体活性区的结合具有良好的稳定性。在均方根偏差(RMSD)和均方根波动(RMSF)计算中,delphinan、β-amyrin和tulipanin与受体结合域亚基1(RBD S1)ACE2蛋白复合物的差异较小。这三种化合物的溶剂可及表面积(SASA)、回旋半径(Rg)、分子表面积(MolSA)和极性表面积(PSA)验证结果同样令人鼓舞。通过使用广义出生和表面分子力学(MM/GBSA)估算配体与蛋白质受体结合的自由能,发现了 100 个结合周期内的方便结合能。综合考虑,这些信息表明,在Euphorbia neriifolia中发现的化学物质更有可能与SARS-CoV-2 ACE2活性位点结合。为确定这些先导化合物的抗 SARS-CoV-2 潜力,应进行体外和体内研究:Islam MN, Pramanik MEA, Hossain MA, et al. Identification of Leading Compounds from Euphorbia Neriifolia (Dudsor) Extracts as a Potential Inhibitor of SARS-CoV-2 ACE2-RBDS1 Receptor Complex:分子对接 ADMET 分析和 MD 模拟研究的启示。Euroasian J Hepato-Gastroenterol 2023;13(2):89-107.
Identification of Leading Compounds from Euphorbia neriifolia (Dudsor) Extracts as a Potential Inhibitor of SARS-CoV-2 ACE2-RBDS1 Receptor Complex: An Insight from Molecular Docking ADMET Profiling and MD-simulation Studies.
Coronavirus disease-19 (COVID-19) are deadly and infectious disease that impacts individuals in a variety of ways. Scientists have stepped up their attempts to find an antiviral drug that targets the spike protein (S) of Angiotensin converting enzyme 2 (ACE2) (receptor protein) as a viable therapeutic target for coronavirus. The most recent study examines the potential antagonistic effects of 17 phytochemicals present in the plant extraction of Euphorbia neriifolia on the anti-SARS-CoV-2 ACE2 protein. Computational techniques like molecular docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET) investigations, and molecular dynamics (MD) simulation analysis were used to investigate the actions of these phytochemicals. The results of molecular docking studies showed that the control ligand (2-acetamido-2-deoxy-β-D-glucopyranose) had a binding potential of -6.2 kcal/mol, but the binding potentials of delphin, β-amyrin, and tulipanin are greater at -10.4, 10.0, and -9.6 kcal/mol. To verify their drug-likeness, the discovered hits were put via Lipinski filters and ADMET analysis. According to MD simulations of the complex run for 100 numbers, delphin binds to the SARS-CoV-2 ACE2 receptor's active region with good stability. In root-mean-square deviation (RMSD) and root mean square fluctuation (RMSF) calculations, delphinan, β-amyrin, and tulipanin showed reduced variance with the receptor binding domain subunit 1(RBD S1) ACE2 protein complex. The solvent accessible surface area (SASA), radius of gyration (Rg), molecular surface area (MolSA), and polar surface area (PSA) validation results for these three compounds were likewise encouraging. The convenient binding energies across the 100 numbers binding period were discovered by using molecular mechanics of generalized born and surface (MM/GBSA) to estimate the ligand-binding free energies to the protein receptor. All things considered, the information points to a greater likelihood of chemicals found in Euphorbia neriifolia binding to the SARS-CoV-2 ACE2 active site. To determine these lead compounds' anti-SARS-CoV-2 potential, in vitro and in vivo studies should be conducted.
How to cite this article: Islam MN, Pramanik MEA, Hossain MA, et al. Identification of Leading Compounds from Euphorbia Neriifolia (Dudsor) Extracts as a Potential Inhibitor of SARS-CoV-2 ACE2-RBDS1 Receptor Complex: An Insight from Molecular Docking ADMET Profiling and MD-simulation Studies. Euroasian J Hepato-Gastroenterol 2023;13(2):89-107.