QcrB inhibition as a potential approach for the treatment of tuberculosis: A review of recent developments, patents, and future directions

Imran, Mohd; Abida, Abida; Alotaibi, Nawaf M.; Thabet, Hamdy Khamees; Alruwaili, Jamal Alhameedi; Asdaq, Syed Mohammed Basheeruddin; Eltaib, Lina; Alshehri, Ahmed; Alsaiari, Ahad Amer; Almehmadi, Mazen; Alshammari, Amal Bader Hommod; Alshammari, Abdulmajeed Mohammed Abdullah

doi:10.1016/j.jiph.2023.04.011

Cited by 4 publications

(2 citation statements)

References 38 publications

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“…Furthermore, to accelerate the investigation of other potent QcrB inhibitors against NTDs, a conclusive summary of a few diverse chemical classes of QcrB inhibitors is highlighted here ( Figure 7 ). 115 …”

Section: Combating Buruli Ulcer Infectionmentioning

confidence: 99%

Unlocking Opportunities for Mycobacterium leprae and Mycobacterium ulcerans

Shyam,

Kumar,

Singh

2024

ACS Infect. Dis.

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In the recent decade, scientific communities have toiled to tackle the emerging burden of drug-resistant tuberculosis (DR-TB) and rapidly growing opportunistic nontuberculous mycobacteria (NTM). Among these, two neglected mycobacteria species of the Acinetobacter family, Mycobacterium leprae and Mycobacterium ulcerans, are the etiological agents of leprosy and Buruli ulcer infections, respectively, and fall under the broad umbrella of neglected tropical diseases (NTDs). Unfortunately, lackluster drug discovery efforts have been made against these pathogenic bacteria in the recent decade, resulting in the discovery of only a few countable hits and majorly repurposing anti-TB drug candidates such as telacebec (Q203), P218, and TB47 for current therapeutic interventions. Major ignorance in drug candidate identification might aggravate the dramatic consequences of rapidly spreading mycobacterial NTDs in the coming days. Therefore, this Review focuses on an up-to-date account of drug discovery efforts targeting selected druggable targets from both bacilli, including the accompanying challenges that have been identified and are responsible for the slow drug discovery. Furthermore, a succinct discussion of the all-new possibilities that could be alternative solutions to mitigate the neglected mycobacterial NTD burden and subsequently accelerate the drug discovery effort is also included. We anticipate that the state-of-the-art strategies discussed here may attract major attention from the scientific community to navigate and expand the roadmap for the discovery of next-generation therapeutics against these NTDs.

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Section: Combating Buruli Ulcer Infectionmentioning

confidence: 99%

Unlocking Opportunities for Mycobacterium leprae and Mycobacterium ulcerans

Shyam,

Kumar,

Singh

2024

ACS Infect. Dis.

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“…ETC in MTB helps move protons and create a proton motive force which assists in generating energy or ATP. Inhibiting this process will lead to a quick loss of cell viability and even death of the MTB (Imran et al, 2023). Targeting this metabolism process can also combat dormant infection and potentially shorten treatment and research duration (Bald et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Virtual Screening of CPP Conjugated Peptide as QcrB BCC Protein Inhibitors of Mycobacterium tuberculosis Bacteria

Muttaqin,

Huang,

Tambunan

2024

OnLine Journal of Biological Sciences

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Tuberculosis is a global leading cause of death, just below COVID-19 and ranked above HIV. This disease is caused by a pathogen called Mycobacterium tuberculosis, which spreads easily through the air and is known to remain latent in most people's bodies, about a quarter of the world's population. The current problems with TB also include two main concerns: The official vaccine is ineffective and the bacteria keep gaining resistance to drugs. In this research, we proposed a strategy to create a new drug to overcome this resistance by simulating it through in silico methods by running molecular docking through Molecular Operating Environment (MOE) software, dynamic simulation through the iMODS website, and pharmacological prediction by comparing it through multiple pharmacophore predictors (AdmetSAR, SwissAdme, and pkCSM). We proposed five peptide drugs (Noopept, Glycyl-L-Proline, Leuteonosticon, Alaptide, dan NNZ-2591) that were then conjugated with a Cell-Penetrating Peptide (CPP) known for its transference prowess, with the receptor of QcrB protein, a complex related to the enzyme responsible for respiration and electron transference in MTB, which can prevent the bacteria development when inhibited. All candidates were picked following the rule of five proposed by Lipinski along with ADME and toxicity evaluation, with models and structures gained from the PubChem database. This research hopes to propose a way of combating drug-resistant TB by using a specified target and CPP for breaking the bacteria's lines of defense.

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