Insilco Peptide Design: A Novel Step Forward to Combat Β-Lactamase Mediated Antimicrobial Resistance

Author(s): Varshaa Arer, Deepesh Nagarajan, Debasish Kar

Antimicrobial resistance (AMR) is one of the most important global health challenges, driven by the ability of bacteria to produce β-lactamase enzymes that hydrolyze β-lactam antibiotics and, therefore, neutralize their effects. This poses a challenge in inhibitor development because the classes A, B, C, and D of β-lactamases show distinct catalytic mechanisms. In this study, in silico approaches involving protein modelling of 20 proteins, and molecular docking have been used to design pentapeptides inhibitors. The study involves specific β-lactamase variants, such as CAE-1 and PER-1 of Class A, VIM-24 and IMP-26 of Class B, CMY-37 and FOX-1 of Class C, and OXA-372 and OXA-50 of Class D β-lactamases. Modelled three-dimensional enzyme structures facilitated the design of peptides against the active site, discovery of high-affinity interactions, and inhibition of enzymatic activity. These results outline the potential of peptide-based therapeutics in overcoming resistance caused by β-lactamase, thereby paving ways to innovative treatments against drug-resistant bacterial infections and ultimately towards improving global public health.