Identification of echinoderm metabolites as potential inhibitors targeting wild-type and mutant forms of Escherichia coli RNA polymerase (RpoB) for tuberculosis treatment.

Autor: Alsulais FM; Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Alhaidhal BA; Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Mothana RA; Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Alanzi AR; Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Aug 30; Vol. 19 (8), pp. e0304587. Date of Electronic Publication: 2024 Aug 30 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0304587
Abstrakt: Tuberculosis (TB) remains a critical global health challenge, with the emergence of drug-resistant strains heightening concerns. The development of effective drugs targeting both wild-type (WT) and mutant Escherichia coli RNA polymerase β subunit (RpoB) is crucial for global TB control, aiming to alleviate TB incidence, mortality, and transmission. This study employs molecular docking and ADMET analyses to screen echinoderm metabolites for their potential inhibition of Escherichia coli RNA polymerase, focusing on wild-type and mutant RpoB variants associated with TB drug resistance. The evaluation of docking results using the glide gscore led to the selection of the top 10 compounds for each protein receptor. Notably, CMNPD2176 demonstrated the highest binding affinity against wild-type RpoB, CMNPD13873 against RpoB D516V mutant, CMNPD2177 against RpoB H526Y mutant, and CMNPD11620 against RpoB S531L mutant. ADMET screening confirmed the therapeutic potential of these selected compounds. Additionally, MM-GBSA binding free energy calculations and molecular dynamics simulations provided further support for the docking investigations. While the results suggest these compounds could be viable for tuberculosis treatment, it is crucial to note that further in-vitro research is essential for the transition from prospective inhibitors to clinical drugs.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Alsulais et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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