In-silico Approach to Combat Methicillin-resistant Staphylococcus aureus: Targeting RelP Protein with Inhibitor Peptide to Mitigate Drug Resistance.

Abstract

Background: Methicillin-resistant Staphylococcus aureus (MRSA), known for its re-sistance to multiple antibiotics, has emerged as a major global health concern. It facilitates biofilm formation under stressful conditions by catalyzing the synthesis of alarmones (p)ppGpp and ppGpp. These alarmones on accumulation lead to biofilm formation and cause resistance towards antibiotics.

Methods: This condition has prompted the exploration of various novel approaches and methodolo-gies to combat MRSA infections. Among these, peptide therapeutics stand out as a promising next-generation treatment option. In this study, ninety antimicrobial peptides were sourced from the anti-microbial peptide database and the other sixty-one peptide sequences were designed using the Pep-draw server. These peptide sequences were screened out using different in-silico tools. The protein-peptide molecular interaction was studied using a molecular docking and molecular dynamic simu-lation technique.

Result: Out of 151 peptide sequences, Pantocin wh-1 emerged as the most promising drug candidate. Both molecular interaction studies and molecular dynamics simulations demonstrated positive re-sults.

Conclusion: Peptide therapeutics is a novel approach researchers are presently exploring as it pro-vides prompt significant results and promotes a new insight towards dealing with conditions like MDR. Pantocin wh-1 is a peptide drug currently listed as an accessible anti-tuberculosis peptide, and this study suggests the repurposing of this drug as a viable treatment option for MRSA infections.