Potential Repurposed Drug Candidates for Tuberculosis Treatment: Progress and Update of Drugs Identified in Over a Decade

Abstract

The devastating impact of Tuberculosis (TB) has been a menace to mankind for decades. The World Health Organization (WHO) End TB Strategy aims to reduce TB mortality up to 95% and 90% of overall TB cases worldwide, by 2035. This incessant urge will be achieved with a breakthrough in either a new TB vaccine or novel drugs with higher efficacy. However, the development of novel drugs is a laborious process involving a timeline of almost 20-30 years with huge expenditure; on the other hand, repurposing previously approved drugs is a viable technique for overcoming current bottlenecks in the identification of new anti-TB agents. The present comprehensive review discusses the progress of almost all the repurposed drugs that have been identified to the present day (∼100) and are in the development or clinical testing phase against TB. We have also emphasized the efficacy of repurposed drugs in combination with already available frontline anti-TB medications along with the scope of future investigations. This study would provide the researchers a detailed overview of nearly all identified anti-TB repurposed drugs and may assist them in selecting the lead compounds for further in vivo/clinical research.

Figure 1

Illustration of the steps involved in the drug repurposing process. Step 1: Screening – identifying potential repurposed drug candidate from a large pool of drugs using appropriate computational or experimental methodologies, Step 2: Shortlisting– selection of potential lead compounds, Step 3: Validation – validating the discovered drug through preclinical and clinical trial investigations.

Figure 2

Potential repurposed drugs under preclinical or clinical stages of investigations against TB. In vitro (n = 32), in vivo (n = 27), clinical studies (n = 21), WHO approved for TB treatment (n = 6). Drug names in orange represent drugs under investigation as adjunctive agents for TB-treatment.

Figure 3

Chemical structures of five WHO approved repurposed drugs for TB treatment.