Bibliographic Details
| Title: |
Anti-bacterial compounds from Indian curry-leaf tree Murraya koenigii have potential to inhibit carbapenem-resistant Streptococcus pneumoniae |
| Authors: |
Soumya Basu, Balaji Veeraraghavan, Anand Anbarasu |
| Source: |
Clinical Epidemiology and Global Health, Vol 28, Iss , Pp 101511- (2024) |
| Publisher Information: |
Elsevier, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Public aspects of medicine |
| Subject Terms: |
Pneumococci, Meropenem, Phytocompounds, Pharmacokinetics, Simulation, Public aspects of medicine, RA1-1270 |
| More Details: |
Problems considered: Spike in the mortality rates due to pneumococcal infections post-COVID-19 has raised clinical concerns globally. β-lactam antibiotic-susceptibility in the causative organism, Streptococcus pneumoniae has been compromised due to non-synonymous single nucleotide polymorphisms (nsSNPs) in different penicillin-binding protein (PBP) targets. Carbapenem-resistant S. pneumoniae strains have further constricted the pharmacologically safe therapeutic options. Methods: In-house sequenced whole genomes of meropenem and cefotaxime resistant Indian and global isolates were used to retrieve parent and mutant proteins. Anti-bacterial phtytochemicals (ABPs) from Indian curry-leaf tree Murraya koenigii were identified using database-mining. ABPs were screeened based on pharmacokinetics, and toxicity profiles. Site-specific molecular docking studies revealed ABPs‘ affinity towards the targets as compared to control drug meropenem. Coarse-grained and normal-mode molecular dynamics simulation further asserted the interactive stability of the chosen compounds. Results: From the whole genomes (n = 28) of meropenem and cefotaxime resistant (MIC ≥0.5 μg/ml) Indian and global isolates, ∼50 nsSNPs in the active-site regions of PBP1A, PBP2B and PBP2X were identified. Based on pharmacological safety and high drug-likeliness, 10 ABPs were funnelled down from 226 ABPs in M. koenigii. A pyrano-carbazole alkaloid koenine was further prioritized as the most efficient candidate based on consistently high binding affinity (binding energies −7.7 to −8.9 kcal/mol), low inhibition constant (0.69–3.5 μM) and low structural fluctuations ( |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2213-3984 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2213398424000071; https://doaj.org/toc/2213-3984 |
| DOI: |
10.1016/j.cegh.2024.101511 |
| Access URL: |
https://doaj.org/article/9d704c61c3fe4e5ba5ebf73fabc4601f |
| Accession Number: |
edsdoj.9d704c61c3fe4e5ba5ebf73fabc4601f |
| Database: |
Directory of Open Access Journals |
