Tuberculosis Drug Discovery and Development 2019
Riccardi, Giovanna (editor)
Sala, Claudia (editor)
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis and still represents one of the global health threats to mankind. The World Health Organization estimated more than 10 million new cases and reported more than 1.5 million deaths in 2019, thus ranking TB among the main causes of death due to a single pathogen. Standard anti-TB therapy includes four first-line antibiotics that should be administered for at least six months. However, in the case of multi- and extensively drug-resistant TB, second-line medications must be used and these frequently cause severe side effects resulting in poor compliance. Developing new anti-TB drug candidates is therefore of outmost importance. In this Special Issue dedicated to Tuberculosis Drug Discovery and Development, we present the main and latest achievements in the fields of drug and target discovery, host-directed therapy, anti-virulence drugs, and describe the development of two advanced compounds: macozinone and delpazolid. In addition, this Special Issue provides an historical perspective focused on Carlo Forlanini, the inventor of pneumothorax for TB treatment, and includes an overview of the state-of-the-art technologies which are being exploited nowadays in TB drug development. Finally, a summary of TB vaccines that are either approved or undergoing clinical trials concludes the Special Issue.
Keywordsmycobacteria; tuberculosis; multi-drug resistance; drug discovery; promiscuous targets; Mycobacterium tuberculosis; rifampin; isoniazid; mechanisms of resistance; mutations; granulomas; caseum; cell envelope; dormancy; delpazolid; macozinone; DprE1 inhibitor; clinical studies; discovery; mode of action; drug resistance; toxicity; target; energy metabolism; electron transport chain; oxidative phosphorylation; bedaquiline; Q203; MID3; pharmacokinetics; pharmacodynamics; drug-drug interactions; in vitro; in vivo; drug development; tuberculosis treatment; biomarkers; drug combination; clinical trial; BCG; tuberculosis vaccines; TBVI; EDCTP; IAVI; CTVD; host-directed therapy; anti-virulence compounds; TB; post-treatment sequelae; surgery; pulmonary rehabilitation; Carlo Forlanini; artificial pneumothorax; n/a; structure-based drug design; target-based drug design; PknB; PknG; DNA gyrase; antibiotic; mycobacterium; genomics; transcriptomics; proteomics; metabolomics; lipidomics; target identification; mechanism of action; antimicrobial drug resistance (AMR); target-based screening; phenotypic screening; antituberculosis agents; antimycobacterial; anti-TB drug pipeline; privileged targets; lead generation
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Publication date and placeBasel, Switzerland, 2020
Research & information: general
Biology, life sciences