{"title":"黄酮类支架对 SARS-CoV-2 3CLpro 的抑制作用：计算和实验研究的启示。","authors":"Nopawit Khamto, Kraikrit Utama, Panida Boontawee, Atchara Janthong, Suriya Tatieng, Supakorn Arthan, Vachira Choommongkol, Padchanee Sangthong, Chavi Yenjai, Nuttee Suree and Puttinan Meepowpan*, ","doi":"10.1021/acs.jcim.3c01477","DOIUrl":null,"url":null,"abstract":"<p >The emergence of the COVID-19 situation has become a global issue due to the lack of effective antiviral drugs for treatment. Flavonoids are a class of plant secondary metabolites that have antiviral activity against SARS-CoV-2 through inhibition of the main protease (3CL<sup>pro</sup>). In this study, 22 flavonoids obtained from natural sources and semisynthetic approaches were investigated for their inhibitory activity against SARS-CoV-2 3CL<sup>pro</sup>, along with cytotoxicity on Vero cells. The protein–ligand interactions were examined using molecular dynamics simulation. Moreover, QSAR analysis was conducted to clarify the structural effects on bioactivity. Accordingly, the <i>in vitro</i> investigation demonstrated that four flavonoids, namely, tectochrysin (<b>7</b>), 6″,6″-dimethylchromeno-[2″,3″:7,8]-flavone (<b>9</b>), panduratin A (<b>19</b>), and genistein (<b>20</b>), showed higher protease inhibitory activity compared to the standard flavonoid baicalein. Finally, our finding suggests that genistein (<b>20</b>), an isoflavone discovered in <i>Millettia brandisiana</i>, has potential for further development as a SARS-CoV-2 3CL<sup>pro</sup> inhibitor.</p>","PeriodicalId":44,"journal":{"name":"Journal of Chemical Information and Modeling ","volume":"64 3","pages":"874–891"},"PeriodicalIF":5.3000,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Inhibitory Activity of Flavonoid Scaffolds on SARS-CoV-2 3CLpro: Insights from the Computational and Experimental Investigations\",\"authors\":\"Nopawit Khamto, Kraikrit Utama, Panida Boontawee, Atchara Janthong, Suriya Tatieng, Supakorn Arthan, Vachira Choommongkol, Padchanee Sangthong, Chavi Yenjai, Nuttee Suree and Puttinan Meepowpan*, \",\"doi\":\"10.1021/acs.jcim.3c01477\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >The emergence of the COVID-19 situation has become a global issue due to the lack of effective antiviral drugs for treatment. Flavonoids are a class of plant secondary metabolites that have antiviral activity against SARS-CoV-2 through inhibition of the main protease (3CL<sup>pro</sup>). In this study, 22 flavonoids obtained from natural sources and semisynthetic approaches were investigated for their inhibitory activity against SARS-CoV-2 3CL<sup>pro</sup>, along with cytotoxicity on Vero cells. The protein–ligand interactions were examined using molecular dynamics simulation. Moreover, QSAR analysis was conducted to clarify the structural effects on bioactivity. Accordingly, the <i>in vitro</i> investigation demonstrated that four flavonoids, namely, tectochrysin (<b>7</b>), 6″,6″-dimethylchromeno-[2″,3″:7,8]-flavone (<b>9</b>), panduratin A (<b>19</b>), and genistein (<b>20</b>), showed higher protease inhibitory activity compared to the standard flavonoid baicalein. Finally, our finding suggests that genistein (<b>20</b>), an isoflavone discovered in <i>Millettia brandisiana</i>, has potential for further development as a SARS-CoV-2 3CL<sup>pro</sup> inhibitor.</p>\",\"PeriodicalId\":44,\"journal\":{\"name\":\"Journal of Chemical Information and Modeling \",\"volume\":\"64 3\",\"pages\":\"874–891\"},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2024-01-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Chemical Information and Modeling \",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.jcim.3c01477\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Chemical Information and Modeling ","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.jcim.3c01477","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Inhibitory Activity of Flavonoid Scaffolds on SARS-CoV-2 3CLpro: Insights from the Computational and Experimental Investigations
The emergence of the COVID-19 situation has become a global issue due to the lack of effective antiviral drugs for treatment. Flavonoids are a class of plant secondary metabolites that have antiviral activity against SARS-CoV-2 through inhibition of the main protease (3CLpro). In this study, 22 flavonoids obtained from natural sources and semisynthetic approaches were investigated for their inhibitory activity against SARS-CoV-2 3CLpro, along with cytotoxicity on Vero cells. The protein–ligand interactions were examined using molecular dynamics simulation. Moreover, QSAR analysis was conducted to clarify the structural effects on bioactivity. Accordingly, the in vitro investigation demonstrated that four flavonoids, namely, tectochrysin (7), 6″,6″-dimethylchromeno-[2″,3″:7,8]-flavone (9), panduratin A (19), and genistein (20), showed higher protease inhibitory activity compared to the standard flavonoid baicalein. Finally, our finding suggests that genistein (20), an isoflavone discovered in Millettia brandisiana, has potential for further development as a SARS-CoV-2 3CLpro inhibitor.
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The Journal of Chemical Information and Modeling publishes papers reporting new methodology and/or important applications in the fields of chemical informatics and molecular modeling. Specific topics include the representation and computer-based searching of chemical databases, molecular modeling, computer-aided molecular design of new materials, catalysts, or ligands, development of new computational methods or efficient algorithms for chemical software, and biopharmaceutical chemistry including analyses of biological activity and other issues related to drug discovery.
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