Potential anti-TB investigational compounds and drugs with repurposing potential in TB therapy: a conspectus

• Published in: Applied microbiology and biotechnology Vol. 104; no. 13; pp. 5633 - 5662
• Main Authors: Adeniji, Adetomiwa A., Knoll, Kirsten E., Loots, Du Toit
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.07.2020; Springer; Springer Nature B.V
• Subjects: Adjuvants, Pharmaceutic - chemistry; Adjuvants, Pharmaceutic - pharmacology; Adjuvants, Pharmaceutic - therapeutic use; Animals; Antibiotics; Antitubercular Agents - chemistry; Antitubercular Agents - pharmacology; Antitubercular Agents - therapeutic use; Auranofin; Bacilli; Biomarkers; Biomedical and Life Sciences; Biotechnology; Diabetes mellitus; Diagnostic systems; Drug approval; Drug development; Drug Evaluation, Preclinical; Drug Repositioning - trends; Drug resistance; Drug resistance in microorganisms; Drug therapy; Drug Therapy, Combination - trends; Drugs; Etoricoxib; Gene expression; Genomes; HIV; Human immunodeficiency virus; Humans; Life Sciences; Metronidazole; Microbial Genetics and Genomics; Microbiology; Mini-Review; Multidrug resistance; Mycobacterium tuberculosis - drug effects; Prodrugs - chemistry; Prodrugs - pharmacology; Prodrugs - therapeutic use; Proteomes; Regulatory approval; Replication; Rifabutin; Therapeutic targets; Therapy; Tuberculosis; Tuberculosis, Multidrug-Resistant - drug therapy; Canada; Anti-tuberculosis therapy; Adjunct drugs; Prodrugs; Drug resistance; Monotherapy; Mycobacterium tuberculosis
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-020-10606-y

The latest WHO report estimates about 1.6 million global deaths annually from TB, which is further exacerbated by drug-resistant (DR) TB and comorbidities with diabetes and HIV. Exiguous dosing, incomplete treatment course, and the ability of the tuberculosis bacilli to tolerate and survive current first-line and second-line anti-TB drugs, in either their latent state or active state, has resulted in an increased prevalence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant TB (TDR-TB). Although a better understanding of the TB microanatomy, genome, transcriptome, proteome, and metabolome, has resulted in the discovery of a few novel promising anti-TB drug targets and diagnostic biomarkers of late, no new anti-TB drug candidates have been approved for routine therapy in over 50 years, with only bedaquiline, delamanid, and pretomanid recently receiving tentative regulatory approval. Considering this, alternative approaches for identifying possible new anti-TB drug candidates, for effectively eradicating both replicating and non-replicating Mycobacterium tuberculosis, are still urgently required. Subsequently, several antibiotic and non-antibiotic drugs with known treatment indications (TB targeted and non-TB targeted) are now being repurposed and/or derivatized as novel antibiotics for possible use in TB therapy. Insights gathered here reveal that more studies focused on drug-drug interactions between licensed and potential lead anti-TB drug candidates need to be prioritized. This write-up encapsulates the most recent findings regarding investigational compounds with promising anti-TB potential and drugs with repurposing potential in TB therapy.