Streptococcosis is a bacterial disease prevalent among warm-water fish, posing a significant threat to the aquatic industry, particularly in tropical regions. The causative agent, Streptococcus agalactiae, is a gram-positive, beta-haemolytic and facultative anaerobe bacterium. The limited use of antibiotics in aquaculture due to bacterial resistance and has heightened the urgency for the discovery of new drugs. This research aims to explore natural product compounds for treating streptococcosis through ligand-based pharmacophore modelling and virtual screening.
By focusing on S. agalactiae , 1061 compounds with Minimum Inhibitory Concentration (MIC) values have been identified using the ChEMBL database. Subsequent filtering by selecting approved drugs and removing duplicate compounds have resulted in a total of 49 active compounds used for modelling. Clustering analysis using LigandScout unveiled 17 distinct clusters, with a notable observation of similar functional groups . Beta-lactam structures, targeting penicillin-binding proteins, were prominent, alongside fluoroquinolones affecting DNA gyrase and topoisomerase IV. Glycopyronase structures exhibited potential in targeting the cell membrane and bacterial ribosome.
The best model as in Figure 1 consists of nine features demonstrating an AUC value of 0.74 with 0.65 sensitivity and 0.73 specificity. Virtual screening was conducted using the natural product NADI database and detecting 77 compounds. The extract of the top 5 compounds in Table 1 has been recorded previously able to inhibit Streptococcus sp indicating the potential of these compounds to be able to work as therapeutic agents for streptococcosis . These findings contribute to ongoing efforts to combat antibiotic resistance in aquaculture, underscoring the importance of innovative drug discovery strategies by using natural product for the sustainable health of aquatic ecosystems.