Opportunities for overcoming tuberculosis: Emerging targets and their inhibitors |
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| Affiliation: | 1. Innovation Institute for Artificial Intelligence in Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China;2. State Key Lab of Computer-aided Design and Computer Graphics (CAD&CG), Zhejiang University, Hangzhou, Zhejiang 310058, China |
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| Abstract: | Tuberculosis (TB), an airborne infectious disease mainly caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of human morbidity and mortality worldwide. Given the alarming rise of resistance to anti-TB drugs and latent TB infection (LTBI), new targets and novel bioactive compounds are urgently needed for the treatment of this disease. We provide an overview of the recent advances in anti-TB drug discovery, emphasizing several newly validated targets for which an inhibitor has been reported in the past five years. Our review presents several attractive directions that have potential for the development of next-generation therapies. |
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| Keywords: | Tuberculosis Drug target Host-directed therapies Drug resistance Virtual screening Computer-aided drug design aaRS" },{" #name" :" keyword" ," $" :{" id" :" k0040" }," $$" :[{" #name" :" text" ," _" :" aminoacyl-tRNA synthetase CADD" },{" #name" :" keyword" ," $" :{" id" :" k0050" }," $$" :[{" #name" :" text" ," _" :" computer-aided drug design CTP" },{" #name" :" keyword" ," $" :{" id" :" k0060" }," $$" :[{" #name" :" text" ," _" :" cytidine triphosphate FBDD" },{" #name" :" keyword" ," $" :{" id" :" k0070" }," $$" :[{" #name" :" text" ," _" :" fragment-based drug discovery FDA" },{" #name" :" keyword" ," $" :{" id" :" k0080" }," $$" :[{" #name" :" text" ," _" :" U.S. Food and Drug Administration HDT" },{" #name" :" keyword" ," $" :{" id" :" k0090" }," $$" :[{" #name" :" text" ," _" :" host-directed therapy half-maximal inhibitory concentration IdeR" },{" #name" :" keyword" ," $" :{" id" :" k0110" }," $$" :[{" #name" :" text" ," _" :" iron-dependent regulator protein LeuRS" },{" #name" :" keyword" ," $" :{" id" :" k0120" }," $$" :[{" #name" :" text" ," _" :" leucyl-tRNA synthetase LTBI" },{" #name" :" keyword" ," $" :{" id" :" k0130" }," $$" :[{" #name" :" text" ," _" :" latent TB infection MDR-TB" },{" #name" :" keyword" ," $" :{" id" :" k0140" }," $$" :[{" #name" :" text" ," _" :" multidrug-resistant TB MIC" },{" #name" :" keyword" ," $" :{" id" :" k0150" }," $$" :[{" #name" :" text" ," _" :" minimal inhibitory concentration Mtb" },{" #name" :" keyword" ," $" :{" id" :" k0160" }," $$" :[{" #name" :" text" ," $$" :[{" #name" :" italic" ," _" :" Mycobacterium tuberculosis PanK" },{" #name" :" keyword" ," $" :{" id" :" k0170" }," $$" :[{" #name" :" text" ," _" :" pantothenate kinase PyrG" },{" #name" :" keyword" ," $" :{" id" :" k0180" }," $$" :[{" #name" :" text" ," _" :" cytidine triphosphate synthetase SAR" },{" #name" :" keyword" ," $" :{" id" :" k0190" }," $$" :[{" #name" :" text" ," _" :" structure-activity relationship SBVS" },{" #name" :" keyword" ," $" :{" id" :" k0200" }," $$" :[{" #name" :" text" ," _" :" structure-based virtual screening TB" },{" #name" :" keyword" ," $" :{" id" :" k0210" }," $$" :[{" #name" :" text" ," _" :" tuberculosis TNF" },{" #name" :" keyword" ," $" :{" id" :" k0220" }," $$" :[{" #name" :" text" ," _" :" tumor necrosis factor Trp" },{" #name" :" keyword" ," $" :{" id" :" k0230" }," $$" :[{" #name" :" text" ," _" :" tryptophan TrpAB" },{" #name" :" keyword" ," $" :{" id" :" k0240" }," $$" :[{" #name" :" text" ," _" :" Trp synthase XDR-TB" },{" #name" :" keyword" ," $" :{" id" :" k0250" }," $$" :[{" #name" :" text" ," _" :" extensively drug-resistant TB |
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