Computational evaluation of efflux pump homologues and lignans as potent inhibitors against multidrug-resistant Salmonella typhi

• DOI: 10.1371/journal.pone.0303285
• Publication Date: 2024-06-25T18:59:26Z
• Authors: Iqra Shafique; Mehak Rafiq; Nosheen Fatima Rana; Farid Menaa; Fatemah Almalki; Alya Aljuaid; Sulaiman Mohammed...; Amenah S. Alotaibi; Madahiah Bint E. ...; Tahreem Tanweer
• Keywords: Efflux; Salmonella enterica; P-glycoprotein

Typhoid fever, caused by Salmonella enterica serovar typhi , presents a substantial global health threat, particularly in regions with limited healthcare infrastructure. The rise of multidrug-resistant strains S. exacerbates this challenge, severely compromising conventional treatment efficacy due to over activity efflux pumps. In our study, comprehensive exploration two fundamental aspects combat MDR is carried out; i.e. employing advanced bioinformatics analyses and AlphaFold AI, We successfully identified characterised putative homologue, ABC-TPA, reminiscent the P-glycoprotein (P-gp) known for its role multidrug resistance diverse pathogens. This discovery provides critical foundation understanding potential mechanisms driving antibiotic . Furthermore, computational methodologies, meticulously assessed lignans, specifically Schisandrin A, B, C, as promising Efflux Pump Inhibitors (EPIs) against P-gp homologue Noteworthy findings revealed robust binding interactions A B target protein, indicating inhibitory capabilities. contrast, C exhibited instability, showing varied effectiveness among evaluated lignans. Pharmacokinetics toxicity predictions underscored favourable attributes including prolonged action duration. high systemic stability demanished profile SA SB present their therapeutic MDR. investigation not only elucidates strategies but also highlights relevance approaches identifying evaluating candidates. These lay future empirical studies address formidable challenges poses clinically significant infectious diseases.