Ebola virus (EBOV) causes a deadly hemorrhagic syndrome in humans with mortality rate up to 90%. First reported in Zaire in 1976, EBOV outbreaks showed a fluctuating trend during time and fora long period it was considered a tragic disease confined to the isolated regions of the African continent where the EBOV fear was perpetuated among the poor communities. The extreme severity of the recent 2014-16 EBOV outbreak in terms of fatality rate and rapid spread out of Africa led to the understanding that EBOV is a global health risk and highlights the necessity to find countermeasures against it. In the recent years, several small molecules have been shown to display in vitro and in vivo efficacy against EBOV and some of them have advanced into clinical trials. In addition, also existing drugs have been tested for their anti-EBOV activity and were shown to be promising candidates. However, despite the constant effort addressed to identify anti-EBOV therapeutics, no approved drugs are available against EBOV yet. In this chapter, we describe the main EBOV life cycle steps, providing a detailed picture of the druggable viral and host targets that have been explored so far by different technologies. We then summarize the small molecules, nucleic acid oligomers, and antibody-based therapies reported to have an effect either in in silico, or in biochemical and cell-based assays or in animal models and clinical trials, listing them according to their demonstrated or putative mechanism of action.
{"title":"Antiviral Agents Against Ebola Virus Infection: Repositioning Old Drugs and Finding Novel Small Molecules.","authors":"Elisa Fanunza, Aldo Frau, Angela Corona, Enzo Tramontano","doi":"10.1016/bs.armc.2018.08.004","DOIUrl":"10.1016/bs.armc.2018.08.004","url":null,"abstract":"<p><p>Ebola virus (EBOV) causes a deadly hemorrhagic syndrome in humans with mortality rate up to 90%. First reported in Zaire in 1976, EBOV outbreaks showed a fluctuating trend during time and fora long period it was considered a tragic disease confined to the isolated regions of the African continent where the EBOV fear was perpetuated among the poor communities. The extreme severity of the recent 2014-16 EBOV outbreak in terms of fatality rate and rapid spread out of Africa led to the understanding that EBOV is a global health risk and highlights the necessity to find countermeasures against it. In the recent years, several small molecules have been shown to display in vitro and in vivo efficacy against EBOV and some of them have advanced into clinical trials. In addition, also existing drugs have been tested for their anti-EBOV activity and were shown to be promising candidates. However, despite the constant effort addressed to identify anti-EBOV therapeutics, no approved drugs are available against EBOV yet. In this chapter, we describe the main EBOV life cycle steps, providing a detailed picture of the druggable viral and host targets that have been explored so far by different technologies. We then summarize the small molecules, nucleic acid oligomers, and antibody-based therapies reported to have an effect either in in silico, or in biochemical and cell-based assays or in animal models and clinical trials, listing them according to their demonstrated or putative mechanism of action.</p>","PeriodicalId":8033,"journal":{"name":"Annual Reports in Medicinal Chemistry","volume":"51 ","pages":"135-173"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10288692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-10-04DOI: 10.1016/BS.ARMC.2017.08.002
Amit Kumar, Jason B White, R. Christie, N. Dimasi, Changshou Gao
{"title":"Antibody-Drug Conjugates","authors":"Amit Kumar, Jason B White, R. Christie, N. Dimasi, Changshou Gao","doi":"10.1016/BS.ARMC.2017.08.002","DOIUrl":"https://doi.org/10.1016/BS.ARMC.2017.08.002","url":null,"abstract":"","PeriodicalId":8033,"journal":{"name":"Annual Reports in Medicinal Chemistry","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/BS.ARMC.2017.08.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42094162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01DOI: 10.1016/BS.ARMC.2017.08.008
P. McEnaney, Christopher G. Parker, Andrew X. Zhang
{"title":"Chapter Thirteen - Antibody-Recruiting Small Molecules: Synthetic Constructs as Immunotherapeutics","authors":"P. McEnaney, Christopher G. Parker, Andrew X. Zhang","doi":"10.1016/BS.ARMC.2017.08.008","DOIUrl":"https://doi.org/10.1016/BS.ARMC.2017.08.008","url":null,"abstract":"","PeriodicalId":8033,"journal":{"name":"Annual Reports in Medicinal Chemistry","volume":"50 1","pages":"481-518"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/BS.ARMC.2017.08.008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54060333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01DOI: 10.1016/BS.ARMC.2017.09.001
L. Urge, J. Alcázar, L. Huck, G. Dormán
{"title":"Chapter Four - Recent Advances of Microfluidics Technologies in the Field of Medicinal Chemistry","authors":"L. Urge, J. Alcázar, L. Huck, G. Dormán","doi":"10.1016/BS.ARMC.2017.09.001","DOIUrl":"https://doi.org/10.1016/BS.ARMC.2017.09.001","url":null,"abstract":"","PeriodicalId":8033,"journal":{"name":"Annual Reports in Medicinal Chemistry","volume":"1 1","pages":"87-147"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/BS.ARMC.2017.09.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54060699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01DOI: 10.1016/BS.ARMC.2017.08.007
Robert Abel, Sathesh Bhat
{"title":"Free Energy Calculation Guided Virtual Screening of Synthetically Feasible Ligand R-Group and Scaffold Modifications: An Emerging Paradigm for Lead Optimization","authors":"Robert Abel, Sathesh Bhat","doi":"10.1016/BS.ARMC.2017.08.007","DOIUrl":"https://doi.org/10.1016/BS.ARMC.2017.08.007","url":null,"abstract":"","PeriodicalId":8033,"journal":{"name":"Annual Reports in Medicinal Chemistry","volume":"50 1","pages":"237-262"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/BS.ARMC.2017.08.007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54060261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01DOI: 10.1016/BS.ARMC.2017.08.009
M. P. Castaldi, A. Zuhl, Piero Ricchiuto, J. A. Hendricks
{"title":"Chapter Ten - Chemical Biology in Drug Discovery","authors":"M. P. Castaldi, A. Zuhl, Piero Ricchiuto, J. A. Hendricks","doi":"10.1016/BS.ARMC.2017.08.009","DOIUrl":"https://doi.org/10.1016/BS.ARMC.2017.08.009","url":null,"abstract":"","PeriodicalId":8033,"journal":{"name":"Annual Reports in Medicinal Chemistry","volume":"50 1","pages":"335-370"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/BS.ARMC.2017.08.009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54060342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01DOI: 10.1016/BS.ARMC.2017.08.001
A. Kooistra, Andrea Volkamer
{"title":"Kinase-Centric Computational Drug Development","authors":"A. Kooistra, Andrea Volkamer","doi":"10.1016/BS.ARMC.2017.08.001","DOIUrl":"https://doi.org/10.1016/BS.ARMC.2017.08.001","url":null,"abstract":"","PeriodicalId":8033,"journal":{"name":"Annual Reports in Medicinal Chemistry","volume":"50 1","pages":"197-236"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/BS.ARMC.2017.08.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54060225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01DOI: 10.1016/BS.ARMC.2017.08.010
J. Liu, S. Harbeson, C. L. Brummel, R. Tung, R. Silverman, D. Doller
{"title":"A Decade of Deuteration in Medicinal Chemistry","authors":"J. Liu, S. Harbeson, C. L. Brummel, R. Tung, R. Silverman, D. Doller","doi":"10.1016/BS.ARMC.2017.08.010","DOIUrl":"https://doi.org/10.1016/BS.ARMC.2017.08.010","url":null,"abstract":"","PeriodicalId":8033,"journal":{"name":"Annual Reports in Medicinal Chemistry","volume":"50 1","pages":"519-542"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/BS.ARMC.2017.08.010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54060374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号