{"title":"COVID-19 Therapies: Protease Inhibitions and Novel Degrader Strategies","authors":"M. Reboud-Ravaux, C. El Amri","doi":"10.3389/fddsv.2022.892057","DOIUrl":null,"url":null,"abstract":"The global spread of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) variants is alarming. In addition to vaccines, effective antiviral agents are urgently needed to combat corona virus disease 2019 (COVID-19). In this review, we will give insights on several canonical approaches using current medicinal chemistry. They target host (TMPRSS2, cathepsins B/L, furin) and viral (3CLpro and PLPro) proteases involved in virus cell entry and virus production, respectively. Innovative mechanisms of drug action are now explored whereby the drug triggers a cellular event that reduces the level of disease-implicated protein or RNA. The potential therapeutic power of induced degradations of viral proteins by PROTACs and of RNA by RIBOTACs for the treatment of COVID-19 will be discussed. Degraders of host cell RNA-binding proteins (RNA-PROTACs) may also constitute a therapeutical opportunity. First applicated to oncology, these novel technologies may be of a particular interest to obtain therapeutics susceptible to act on mutated viruses.","PeriodicalId":73080,"journal":{"name":"Frontiers in drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2022-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in drug discovery","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3389/fddsv.2022.892057","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 2
Abstract
The global spread of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) variants is alarming. In addition to vaccines, effective antiviral agents are urgently needed to combat corona virus disease 2019 (COVID-19). In this review, we will give insights on several canonical approaches using current medicinal chemistry. They target host (TMPRSS2, cathepsins B/L, furin) and viral (3CLpro and PLPro) proteases involved in virus cell entry and virus production, respectively. Innovative mechanisms of drug action are now explored whereby the drug triggers a cellular event that reduces the level of disease-implicated protein or RNA. The potential therapeutic power of induced degradations of viral proteins by PROTACs and of RNA by RIBOTACs for the treatment of COVID-19 will be discussed. Degraders of host cell RNA-binding proteins (RNA-PROTACs) may also constitute a therapeutical opportunity. First applicated to oncology, these novel technologies may be of a particular interest to obtain therapeutics susceptible to act on mutated viruses.
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