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Review
. 2021 Apr 21;13(5):592.
doi: 10.3390/pharmaceutics13050592.

Recent Progress and Challenges for Drug-Resistant Tuberculosis Treatment

Filia Stephanie  1 , Mutiara Saragih  1 , Usman Sumo Friend Tambunan  1
Affiliations
Review

Recent Progress and Challenges for Drug-Resistant Tuberculosis Treatment

Filia Stephanie et al. Pharmaceutics. .

Abstract

Control of Mycobacterium tuberculosis infection continues to be an issue, particularly in countries with a high tuberculosis (TB) burden in the tropical and sub-tropical regions. The effort to reduce the catastrophic cost of TB with the WHO's End TB Strategy in 2035 is still obstructed by the emergence of drug-resistant TB (DR-TB) cases as result of various mutations of the MTB strain. In the approach to combat DR-TB, several potential antitubercular agents were discovered as inhibitors for various existing and novel targets. Host-directed therapy and immunotherapy also gained attention as the drug-susceptibility level of the pathogen can be reduced due to the pathogen's evolutionary dynamics. This review is focused on the current progress and challenges in DR-TB treatment. We briefly summarized antitubercular compounds that are under development and trials for both DR-TB drug candidates and host-directed therapy. We also highlighted several problems in DR-TB diagnosis, the treatment regimen, and drug discovery that have an impact on treatment adherence and treatment failure.

Keywords: drug discovery and development; drug-resistance; host-directed therapy; tuberculosis.

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Conflict of interest statement

The authors declare no conflict of interests.

Figures

Figure 1
Figure 1
Structure of (A) moxifloxacin, (B) gatifloxacin, and (C) levofloxacin.
Figure 2
Figure 2
Levofloxacin (blue) in DNA gyrase subunit A (gray ribbon) and subunit B (green ribbon) (PDBID: 5BTI).
Figure 3
Figure 3
Rifampicin (blue) in MTB RNA polymerase subunit β (gray ribbon) (PDBID: 5UH6).
Figure 4
Figure 4
Structure of (A) linezolid, (B) delpazolid, (C) sutezolid, and (D) TBI-223.
Figure 5
Figure 5
Structure of (A) delamanid and (B) pretomanid.
Figure 6
Figure 6
Bedaquiline (blue) in mycobacterial ATP synthase subunit C (gray ribbon) (PDBID: 4V1F).
Figure 7
Figure 7
Structure of (A) bedaquiline, (B) TBAJ-587, and (C) TBAJ-876.
Figure 8
Figure 8
Structure of (A) BTZ-043 and (B) macozinone.
Figure 9
Figure 9
Structure of (A) nitazoxanide and (B) sanfetrinem.
Figure 10
Figure 10
Structure of (A) TBI-7371 and (B) OPC-167832.
See this image and copyright information in PMC

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