Identification of Novel PBP2B Protein Inhibitors against Streptococcus pneumoniae in Marine Natural Products using an In-Silico Approach

Abstract

Background: The aim of this research is to identify marine natural compounds derived from green, red, and brown algae that might possibly inhibit the Penicillin-Binding Proteins (PBPs) protein, which is responsible for the development of antibiotic resistance in Streptococcus pneumoniae (mutated resistant 5204-PBP2B strain). We obtained this by using virtual screening and molecular docking. In AutoDock Vina and the Schrodinger suite software, we screened a library of marine natural chemicals and discovered four intriguing candidates that had strong binding affinities to the active region of the PBPs protein. Based on our findings, four naturally occurring marine chemicals show great promise as new inhibitors of S. pneumoniae 5204-PBP2B protein. These discoveries reveal important new information on the potential application of marine natural products as a source of new drugs to combat antibiotic resistance in Streptococcus pneumoniae and other bacterial infections. Methods: The 3318 compounds in the Comprehensive Marine Natural Products Database (CMNPD) derived from green algae (293 compounds), brown algae (1212 compounds) and red algae (1813 compounds) were taken into consideration for this study. Through virtual screening and molecular docking investigations, we found the optimum compounds for the Penicillin-Binding Proteins (PBPs) protein in Streptococcus pneumoniae. Utilizing AutoDock Vina and Schrodinger Suite software, the 5204-PBP2B protein selected for this investigation was examined. The structure and binding interaction have been displayed using PyMOL software. Results: Through virtual screening and molecular docking investigations for the 5204-PBP2B protein in Streptococcus pneumoniae, we were able to identify four marine natural products that are present in brown algae from the Comprehensive Marine Natural Products Database. Conclusion: The study has indicated that the main cause of bacterial resistance to antibiotics is 5204-PBP2B in S. pneumoniae. This study's methodology has been shown to be effective in identifying four strong inhibitors of the CMNPD. In this work, potent molecules from CMNPD compounds were screened using the 3D structure of mutated resistant 5204 strain, named 5204- PBP2B (PDB ID: 2WAE) of S. pneumoniae. Out of 3318 compounds that showed strong interactions with PBP2B, docking studies revealed that four of the compounds were inhibitory for the protein and could be used to treat PBP2B. These four marine products were selected as a result of our earlier research on Klebsiella pneumonia’s New Delhi metallo-β-lactamase-1 (NDM-1) protein. This study thus reveals the importance of marine natural products for improving the drug development process, as well as the ability of four marine products generated from brown algae to inhibit both the NDM-1 protein of Klebsiella pneumoniae and the 5204-PBP2B protein in Streptococcus pneumoniae. It is also possible to expand this approach by investigating how different receptor inhibitors interact in a lab setting. Potential inhibitors can be discovered by evaluating the biological activity of the drugs and applying virtual screening and molecular docking techniques.