Antituberculosis Drug Repurposing: A New Hope for Tackling Multi-Challenging TB in Timely Manner

Abstract

Tuberculosis still stands as the world’s leading infectious disease as 1/4th of the world’s population harbors Latent TB infection (LTBI) > 10 million develops active TB and ~ 1.5 million people die per year. Approximately 4,65,000 people fell ill with multidrug or rifampicin-resistant tuberculosis (MDR/RR-TB)/year. This deadly TB scenario demands new TB drug regimens to tackle global infection reservoir, and worldwide spread of drug resistance and DS TB. Successful entry of single new drug into market is much complicated mission owing to time, cost, efficacy, and safety issues. Therefore, drug repurposing seems one reliable hope to meet the challenges of modern TB drug discovery timely, as it starts with examining market acclaimed drugs against other diseases for their efficacies against tuberculosis avoiding several lengthy and costly steps required for new molecules. Several drugs have been identified, which show potential for TB treatment. There is need for careful consideration of various trial designs to ensure that TB phase III trials are initiated for fruitful development of new TB treatment regimens. TB drug repurposing will not only give fast track novel drugs but will also serve to identify new targets for future development in cost-effective manner.

An overview of current strategies and future prospects in drug repurposing in tuberculosis

“…Small libraries of failed or authorized compounds with some understanding of their safety or mechanism of action (MoA) are used for experimental screening to find a repurposing candidate. On the other hand, drug discovery screens look for fresh candidates (hits) utilizing specialized screening equipment and compound libraries comprising millions of compounds [9]. In contrast to conventional methodologies, in silico approaches and high-performance computing offer an interesting alternative to finding new or repurposed candidates given the high development costs and high attrition rates [10].…”

Repurposing of anti-malarial drugs for the treatment of tuberculosis: realistic strategy or fanciful dead end?

“…Drug repurposing initiatives targeting new antimicrobial treatments typically begin with in vitro assays or, in more advanced stages, with pre-clinical rodent models. This approach has been a common thread in both bacterial and viral research [6][7][8][9]. However, the potential for an enormous disconnect between laboratory promise and clinical efficacy is highlighted using chloroquine and ivermectin in treating SARS-CoV-2.…”