Potential Therapeutic Candidates against Chlamydia pneumonia Discovered and Developed In Silico Using Core Proteomics and Molecular Docking and Simulation-Based Approaches

Abstract

Chlamydia pneumonia, a species of the family Chlamydiacea, is a leading cause of pneumonia. Failure to eradicate C. pneumoniae can lead to chronic infection, which is why it is also considered responsible for chronic inflammatory disorders such as asthma, arthritis, etc. There is an urgent need to tackle the major concerns arising due to persistent infections caused by C. pneumoniae as no FDA-approved drug is available against this chronic infection. In the present study, an approach named subtractive proteomics was employed to the core proteomes of five strains of C. pneumonia using various bioinformatic tools, servers, and software. However, 958 non-redundant proteins were predicted from the 4754 core proteins of the core proteome. BLASTp was used to analyze the non-redundant genes against the proteome of humans, and the number of potential genes was reduced to 681. Furthermore, based on subcellular localization prediction, 313 proteins with cytoplasmic localization were selected for metabolic pathway analysis. Upon subsequent analysis, only three cytoplasmic proteins, namely 30S ribosomal protein S4, 4-hydroxybenzoate decarboxylase subunit C, and oligopeptide binding protein, were identified, which have the potential to be novel drug target candidates. The Swiss Model server was used to predict the target proteins’ three-dimensional (3D) structure. The molecular docking technique was employed using MOE software for the virtual screening of a library of 15,000 phytochemicals against the interacting residues of the target proteins. Molecular docking experiments were also evaluated using molecular dynamics simulations and the widely used MM-GBSA and MM-PBSA binding free energy techniques. The findings revealed a promising candidate as a novel target against C. pneumonia infections.

Therapeutic target mapping from the genome of Kingella negevensis and biophysical inhibition assessment through PNP synthase binding with traditional medicinal compounds

“…This approach has previously been implemented for identifying therapeutic targets in drug resistant Salmonella typhi [ 10 ], Enterobacteriacea family [ 11 ], Bacillus sp. [ 12 ], Chlamydia pneumoniae [ 13 ] etc. Main principle is application of the ‘essentiality & selectivity criteria’, where a gene product presence should be necessary for the bacterial survival and lacking in host.…”

In Silico Screening of Leguminosae Phytochemicals as Potential Inhibitors of Lung Cancer: A Structure-Based Multi-Targeted Molecular Docking Analysis

“…These technologies are cost-effective and time-saving compared to traditional methods, making them valuable tools in the drug design process. 34 Certain leguminous plants contain compounds such as flavonoids, isoflavones, and saponins. These compounds have demonstrated anti-inflammatory and antioxidant properties, and have the potential to be used as anticancer agents.…”