Exploration of CviR-mediated quorum sensing inhibitors from Cladosporium spp. against Chromobacterium violaceum through computational studies

Abstract

An opportunistic human pathogenic bacterium, Chromobacterium violaceum resists the potency of most antibiotics by exploiting the quorum sensing system within their community to control virulence factor expression. Therefore, blocking the quorum sensing mechanism could help to treat several infectious caused by this organism. The quorum sensing receptor (CviR) of C. violaceum was used as a model target in the current investigation to identify potentially novel quorum sensing inhibitors from Cladosporium spp. through in silico computational approaches. The molecular docking results confirmed the anti-quorum sensing potential of bioactive compounds from Cladosporium spp. through binding to CviR with varying docking scores between – 5.2 and – 9.5 kcal/mol. Relative to the positive control [Azithromycin (– 7.4 kcal/mol)], the top six metabolites of Cladosporium spp. had higher docking scores and were generally greater than – 8.5 kcal/mol. The thermodynamic stability and binding affinity refinement of top-ranked CviR inhibitors were further studied through a 160 ns molecular dynamic (MD) simulation. The Post-MD simulation analysis confirmed the top-ranked compounds' affinity, stability, and biomolecular interactions with CviR at 50 ns, 100 ns, and 160 ns with Coniochaetone K of the Cladosporium spp. having the highest binding free energy (– 30.87 kcal/mol) and best interactions (two consistent hydrogen bond contact) following the 160 ns simulation. The predicted pharmacokinetics properties of top selected compounds point to their drug likeliness, potentiating their chance as a possible drug candidate. Overall, the top-ranked compounds from Cladosporium spp., especially Coniochaetone K, could be identified as potential C. violaceum CviR inhibitors. The development of these compounds as broad-spectrum antibacterial medicines is thus possible in the future following the completion of further preclinical and clinical research.

Secondary metabolites of Trichoderma spp. as EGFR tyrosine kinase inhibitors: Evaluation of anticancer efficacy through computational approach

“…Further, the MM-PBSA analysis of the lead metabolite (Aspochalasin M)/ standard inhibitor (Erlotinib)–bound EGFR tyrosine kinase domain complex trajectories of the last 20 ns (80–100 ns) MD simulations were performed to determine the complex’s thermodynamics parameters such as van der Waals energy (E vdw ), electrostatic energy (E Elec ), polar solvation energy (ΔE Polar ), SASA energy and binding free energy (ΔE Binding ), all of which are expressed as kcal/mol ( Table 3 ). Compared to other energies, van der Waals energy was the main driver of complex formation [ 47 , 48 ] and it can be inferred that the binding energy and van der Waals energy significantly influenced the complex formation. Based on energy calculation, the expected outcomes were largely beneficial from an energetic standpoint.…”

Computational exploration of Picrasma quassioides compounds as CviR-mediated quorum sensing inhibitors against Chromobacterium violaceum

“…The re-docking study confirmed that the potential compounds and positive control showed the same binding energy with RMSD values between ≤2.0 Å, which agrees with the findings of Ramírez and Caballero (2018) . Recently, Murali et al (2023) have intended to identify the effective inhibitors of quorum sensing from 123 bioactive compounds of Cladosporium spp. against C. violaceum through computational studies and noted that six compounds had higher docking score than Azithromycin, suggesting their strong affinity towards the CviR protein.…”

Exploration of Type III effector Xanthomonas outer protein Q (XopQ) inhibitor from Picrasma quassioides as an antibacterial agent using chemoinformatics analysis

“…In addition, the predicted toxicity parameters of the drug were AMES toxicity, maximum human tolerated dose, human Ether-à-go-go Related Gene (hERG) I and II inhibitors, oral rat acute toxicity (LD 50 ) and chronic toxicity (LOAEL), hepatotoxicity, skin sensitization, Tetrahymena pyriformis toxicity and minnow toxicity. Ames test is a robust bacterial bioassay used to identify possible carcinogens by studying their mutagenic effect on bacteria [ 70 , 71 ]. The predicted results suggested that Kumudine B was expected to be AMES test negative; thus, it was non-mutagenic and may not act as a carcinogen compared to Streptomycin.…”