{"title":"研究药材中的大黄素衍生物对 SARS-CoV-2 的抗药性","authors":"Talambedu Usha , Kadabagere Narayanaswamy Hemavathi , Arvind Kumar Goyal , C.S. Abhinand , S. Dhivya , A. Cholarajan , Neelu Joshi , Dinesh Babu , Sushil Kumar Middha","doi":"10.1016/j.kjs.2024.100265","DOIUrl":null,"url":null,"abstract":"<div><p>SARS-CoV-2 continues to mutate and circulate at alarming levels around the world and is exemplified by the emergence of the new variant JN.1. The emergence of novel SARS-CoV variants underscores the urgency for the development of new drugs. Phytochemicals, known for their safety and efficacy, have been widely used to address various ailments. This study aims at identifying the anti-SARS-CoV potential of emodin, a bioactive anthraquinone, and its derivatives. Key proteins, including hemagglutinin-esterase (HE), papain-like protease (PL<sup>pro</sup>), major protease (3CL<sup>pro</sup>), non-structural protein (nsp3) and spike protein(S) of SARS-CoV, were used as protein targets for the virtual screening of 110 emodin derivatives (ED) and remdesivir a proven antiviral drug. Among the 110 derivatives, ED21, ED25, ED5 inhibited HE, 3CL<sup>pro</sup> and S protein, respectively. ED29 inhibited both PL<sup>pro</sup> and nsp3 with high binding affinity. Similar receptor binding sites were occupied by remdesivir and emodin derivatives. These emodin derivatives are bound to similar amino acids in receptors as compared to remdesivir. Further dynamic simulations studies with ED21-HE, ED25-3CL<sup>pro</sup>, ED5-S, ED29-PL<sup>pro</sup> and ED29-nsp3 complexes showed all of them are stable with minimum root mean square deviation (RMSD), root mean square fluctuation (RMSF), solvent-accessible surface area (SASA) and radius of gyration (Rg) and are comparable to APO protein. All the ligands accepted Lipinski's rule of five. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis revealed only ED21 and ED5 as promising druglike candidates that can have high therapeutic value and no side effects. These <em>in-silico</em> findings contribute to the development of potent SARS-CoV-2 inhibitors, potentially advancing the quest for effective antiviral drugs.</p></div>","PeriodicalId":17848,"journal":{"name":"Kuwait Journal of Science","volume":null,"pages":null},"PeriodicalIF":1.2000,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2307410824000907/pdfft?md5=d4c4f8625b9851c61fd38f16bc00a7b6&pid=1-s2.0-S2307410824000907-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Investigating emodin derivatives against SARS-CoV-2 found in medicinal herbs\",\"authors\":\"Talambedu Usha , Kadabagere Narayanaswamy Hemavathi , Arvind Kumar Goyal , C.S. Abhinand , S. Dhivya , A. Cholarajan , Neelu Joshi , Dinesh Babu , Sushil Kumar Middha\",\"doi\":\"10.1016/j.kjs.2024.100265\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>SARS-CoV-2 continues to mutate and circulate at alarming levels around the world and is exemplified by the emergence of the new variant JN.1. The emergence of novel SARS-CoV variants underscores the urgency for the development of new drugs. Phytochemicals, known for their safety and efficacy, have been widely used to address various ailments. This study aims at identifying the anti-SARS-CoV potential of emodin, a bioactive anthraquinone, and its derivatives. Key proteins, including hemagglutinin-esterase (HE), papain-like protease (PL<sup>pro</sup>), major protease (3CL<sup>pro</sup>), non-structural protein (nsp3) and spike protein(S) of SARS-CoV, were used as protein targets for the virtual screening of 110 emodin derivatives (ED) and remdesivir a proven antiviral drug. Among the 110 derivatives, ED21, ED25, ED5 inhibited HE, 3CL<sup>pro</sup> and S protein, respectively. ED29 inhibited both PL<sup>pro</sup> and nsp3 with high binding affinity. Similar receptor binding sites were occupied by remdesivir and emodin derivatives. These emodin derivatives are bound to similar amino acids in receptors as compared to remdesivir. Further dynamic simulations studies with ED21-HE, ED25-3CL<sup>pro</sup>, ED5-S, ED29-PL<sup>pro</sup> and ED29-nsp3 complexes showed all of them are stable with minimum root mean square deviation (RMSD), root mean square fluctuation (RMSF), solvent-accessible surface area (SASA) and radius of gyration (Rg) and are comparable to APO protein. All the ligands accepted Lipinski's rule of five. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis revealed only ED21 and ED5 as promising druglike candidates that can have high therapeutic value and no side effects. These <em>in-silico</em> findings contribute to the development of potent SARS-CoV-2 inhibitors, potentially advancing the quest for effective antiviral drugs.</p></div>\",\"PeriodicalId\":17848,\"journal\":{\"name\":\"Kuwait Journal of Science\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.2000,\"publicationDate\":\"2024-05-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2307410824000907/pdfft?md5=d4c4f8625b9851c61fd38f16bc00a7b6&pid=1-s2.0-S2307410824000907-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Kuwait Journal of Science\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2307410824000907\",\"RegionNum\":4,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Kuwait Journal of Science","FirstCategoryId":"103","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2307410824000907","RegionNum":4,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
Investigating emodin derivatives against SARS-CoV-2 found in medicinal herbs
SARS-CoV-2 continues to mutate and circulate at alarming levels around the world and is exemplified by the emergence of the new variant JN.1. The emergence of novel SARS-CoV variants underscores the urgency for the development of new drugs. Phytochemicals, known for their safety and efficacy, have been widely used to address various ailments. This study aims at identifying the anti-SARS-CoV potential of emodin, a bioactive anthraquinone, and its derivatives. Key proteins, including hemagglutinin-esterase (HE), papain-like protease (PLpro), major protease (3CLpro), non-structural protein (nsp3) and spike protein(S) of SARS-CoV, were used as protein targets for the virtual screening of 110 emodin derivatives (ED) and remdesivir a proven antiviral drug. Among the 110 derivatives, ED21, ED25, ED5 inhibited HE, 3CLpro and S protein, respectively. ED29 inhibited both PLpro and nsp3 with high binding affinity. Similar receptor binding sites were occupied by remdesivir and emodin derivatives. These emodin derivatives are bound to similar amino acids in receptors as compared to remdesivir. Further dynamic simulations studies with ED21-HE, ED25-3CLpro, ED5-S, ED29-PLpro and ED29-nsp3 complexes showed all of them are stable with minimum root mean square deviation (RMSD), root mean square fluctuation (RMSF), solvent-accessible surface area (SASA) and radius of gyration (Rg) and are comparable to APO protein. All the ligands accepted Lipinski's rule of five. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis revealed only ED21 and ED5 as promising druglike candidates that can have high therapeutic value and no side effects. These in-silico findings contribute to the development of potent SARS-CoV-2 inhibitors, potentially advancing the quest for effective antiviral drugs.
期刊介绍:
Kuwait Journal of Science (KJS) is indexed and abstracted by major publishing houses such as Chemical Abstract, Science Citation Index, Current contents, Mathematics Abstract, Micribiological Abstracts etc. KJS publishes peer-review articles in various fields of Science including Mathematics, Computer Science, Physics, Statistics, Biology, Chemistry and Earth & Environmental Sciences. In addition, it also aims to bring the results of scientific research carried out under a variety of intellectual traditions and organizations to the attention of specialized scholarly readership. As such, the publisher expects the submission of original manuscripts which contain analysis and solutions about important theoretical, empirical and normative issues.