C. Cortés-García, L. Chacón-García, Jorge Emmanuel Mejía-Benavides, E. Díaz-Cervantes
{"title":"使用1,5-二取代四唑-1,2,3-三唑的杂交衍生物处理严重急性呼吸系统综合征冠状病毒2型主要蛋白酶:一种计算机分析","authors":"C. Cortés-García, L. Chacón-García, Jorge Emmanuel Mejía-Benavides, E. Díaz-Cervantes","doi":"10.7717/peerj-pchem.10","DOIUrl":null,"url":null,"abstract":"In regard to the actual public health global emergency and, based on the state of the art about the ways to inhibit the SARS-CoV-2 treating the COVID19, a family of 1,5-disubstituted tetrazole-1,2,3-triazoles, previously synthesized, have been evaluated through in silico assays against the main protease of the mentioned virus (CoV-2-MPro). The results show that three of these compounds present a more favorable interaction with the selected target than the co-crystallized molecule, which is a peptide-like derivative. It was also found that also hydrophobic interactions play a key role in the ligand-target molecular couplings, due to the higher hydrophobic surfaces into the active site. Finally, a pharmacophore model has been proposed based on the results below, and a family of 1,5-DT derivatives has been designed and tested with the same methods employed in this work. It was concluded that the compound with the isatin as a substituent (P8) present the higher ligand-target interaction, which makes this a strong drug candidate against COVID19, due can inhibit the CoV-2-MProprotein.","PeriodicalId":93220,"journal":{"name":"PeerJ physical chemistry","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2020-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"16","resultStr":"{\"title\":\"Tackling the SARS-CoV-2 main protease using hybrid derivatives of 1,5-disubstituted tetrazole-1,2,3-triazoles: an in silico assay\",\"authors\":\"C. Cortés-García, L. Chacón-García, Jorge Emmanuel Mejía-Benavides, E. Díaz-Cervantes\",\"doi\":\"10.7717/peerj-pchem.10\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"In regard to the actual public health global emergency and, based on the state of the art about the ways to inhibit the SARS-CoV-2 treating the COVID19, a family of 1,5-disubstituted tetrazole-1,2,3-triazoles, previously synthesized, have been evaluated through in silico assays against the main protease of the mentioned virus (CoV-2-MPro). The results show that three of these compounds present a more favorable interaction with the selected target than the co-crystallized molecule, which is a peptide-like derivative. It was also found that also hydrophobic interactions play a key role in the ligand-target molecular couplings, due to the higher hydrophobic surfaces into the active site. Finally, a pharmacophore model has been proposed based on the results below, and a family of 1,5-DT derivatives has been designed and tested with the same methods employed in this work. It was concluded that the compound with the isatin as a substituent (P8) present the higher ligand-target interaction, which makes this a strong drug candidate against COVID19, due can inhibit the CoV-2-MProprotein.\",\"PeriodicalId\":93220,\"journal\":{\"name\":\"PeerJ physical chemistry\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2020-06-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"16\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"PeerJ physical chemistry\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.7717/peerj-pchem.10\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"PeerJ physical chemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.7717/peerj-pchem.10","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Tackling the SARS-CoV-2 main protease using hybrid derivatives of 1,5-disubstituted tetrazole-1,2,3-triazoles: an in silico assay
In regard to the actual public health global emergency and, based on the state of the art about the ways to inhibit the SARS-CoV-2 treating the COVID19, a family of 1,5-disubstituted tetrazole-1,2,3-triazoles, previously synthesized, have been evaluated through in silico assays against the main protease of the mentioned virus (CoV-2-MPro). The results show that three of these compounds present a more favorable interaction with the selected target than the co-crystallized molecule, which is a peptide-like derivative. It was also found that also hydrophobic interactions play a key role in the ligand-target molecular couplings, due to the higher hydrophobic surfaces into the active site. Finally, a pharmacophore model has been proposed based on the results below, and a family of 1,5-DT derivatives has been designed and tested with the same methods employed in this work. It was concluded that the compound with the isatin as a substituent (P8) present the higher ligand-target interaction, which makes this a strong drug candidate against COVID19, due can inhibit the CoV-2-MProprotein.