Brandon H. Adame-Velasco, Pablo Octavio-Aguilar, Luis H. Mendoza-Huizar, Liliana M. Aguilar-Castro
{"title":"将 SARS-CoV-2 穗状糖蛋白作为治疗开发的分子靶点进行评估","authors":"Brandon H. Adame-Velasco, Pablo Octavio-Aguilar, Luis H. Mendoza-Huizar, Liliana M. Aguilar-Castro","doi":"10.36922/itps.1651","DOIUrl":null,"url":null,"abstract":"The SARS-CoV-2 virus gains entry into host cells by binding its spike glycoprotein (S-glycoprotein) to the angiotensin 2 receptor. This viral protein contains several conserved regions, such as the receptor binding domain region, making it an ideal target for treating COVID-19. Notably, the majority of existing vaccines elicit antigenic reaction by targeting this protein epitope. This study evaluated the binding affinities of 44 different drugs against the SARS-CoV-2 S-glycoprotein, considering their toxicity profiles and previous clinical studies at different testing stages. Our results revealed that maraviroc and estradiol benzoate exhibited high affinities (−7.7 and −7.6 kcal mol−1, respectively), while other ligands, such as indinavir and ritonavir, showed affinity at lower levels. Among the drugs with high affinity, toxicity levels ranged from harmful if swallowed (300 mg/kg < LD50 < 2000 mg/kg) to non-toxic (LD50 > 5000 mg/kg), with only three having undergone clinical testing, yielding promising or controversial results. Furthermore, emtricitabine and docosanol, previously explored as COVID-19 treatments, exhibited the lowest affinities (−4.7 and −3.9 kcal mol−1, respectively), with associated harmful effects if swallowed. These results provide essential information about drug interaction against the SARS-CoV-2 S-glycoprotein and potential treatment pathways for COVID-19.","PeriodicalId":13673,"journal":{"name":"INNOSC Theranostics and Pharmacological Sciences","volume":"101 41","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Evaluating the SARS-CoV-2 spike glycoprotein as a molecular target for therapeutic development\",\"authors\":\"Brandon H. Adame-Velasco, Pablo Octavio-Aguilar, Luis H. Mendoza-Huizar, Liliana M. Aguilar-Castro\",\"doi\":\"10.36922/itps.1651\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The SARS-CoV-2 virus gains entry into host cells by binding its spike glycoprotein (S-glycoprotein) to the angiotensin 2 receptor. This viral protein contains several conserved regions, such as the receptor binding domain region, making it an ideal target for treating COVID-19. Notably, the majority of existing vaccines elicit antigenic reaction by targeting this protein epitope. This study evaluated the binding affinities of 44 different drugs against the SARS-CoV-2 S-glycoprotein, considering their toxicity profiles and previous clinical studies at different testing stages. Our results revealed that maraviroc and estradiol benzoate exhibited high affinities (−7.7 and −7.6 kcal mol−1, respectively), while other ligands, such as indinavir and ritonavir, showed affinity at lower levels. Among the drugs with high affinity, toxicity levels ranged from harmful if swallowed (300 mg/kg < LD50 < 2000 mg/kg) to non-toxic (LD50 > 5000 mg/kg), with only three having undergone clinical testing, yielding promising or controversial results. Furthermore, emtricitabine and docosanol, previously explored as COVID-19 treatments, exhibited the lowest affinities (−4.7 and −3.9 kcal mol−1, respectively), with associated harmful effects if swallowed. These results provide essential information about drug interaction against the SARS-CoV-2 S-glycoprotein and potential treatment pathways for COVID-19.\",\"PeriodicalId\":13673,\"journal\":{\"name\":\"INNOSC Theranostics and Pharmacological Sciences\",\"volume\":\"101 41\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-03-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"INNOSC Theranostics and Pharmacological Sciences\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.36922/itps.1651\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"INNOSC Theranostics and Pharmacological Sciences","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.36922/itps.1651","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Evaluating the SARS-CoV-2 spike glycoprotein as a molecular target for therapeutic development
The SARS-CoV-2 virus gains entry into host cells by binding its spike glycoprotein (S-glycoprotein) to the angiotensin 2 receptor. This viral protein contains several conserved regions, such as the receptor binding domain region, making it an ideal target for treating COVID-19. Notably, the majority of existing vaccines elicit antigenic reaction by targeting this protein epitope. This study evaluated the binding affinities of 44 different drugs against the SARS-CoV-2 S-glycoprotein, considering their toxicity profiles and previous clinical studies at different testing stages. Our results revealed that maraviroc and estradiol benzoate exhibited high affinities (−7.7 and −7.6 kcal mol−1, respectively), while other ligands, such as indinavir and ritonavir, showed affinity at lower levels. Among the drugs with high affinity, toxicity levels ranged from harmful if swallowed (300 mg/kg < LD50 < 2000 mg/kg) to non-toxic (LD50 > 5000 mg/kg), with only three having undergone clinical testing, yielding promising or controversial results. Furthermore, emtricitabine and docosanol, previously explored as COVID-19 treatments, exhibited the lowest affinities (−4.7 and −3.9 kcal mol−1, respectively), with associated harmful effects if swallowed. These results provide essential information about drug interaction against the SARS-CoV-2 S-glycoprotein and potential treatment pathways for COVID-19.