In Silico Characterization of a Key Cell Wall Enzyme for targeting Methicillin-Resistant Staphylococcus aureus using Bioactive compoundsderived from Haematococcus pluvialis

Methicillin-resistant Staphylococcus aureus (MRSA) is a critical global problem in case of infection due to its multidrug resistance and adaptive nature. Polyisoprenyl-teichoic acid--peptidoglycan teichoic acid transferase (PTA), an essential enzyme for biosynthesis of teichoic acid is present in almost all of the gram-positive species, especially S. aureus. A biocompatible gel-patch formulated using acetone extract of microalgae Haematococcus pluvialis was developed and evaluated for its favourable physicochemical properties such as moisture retention and thickness. Antioxidant activity of the patch and extract was assessed via DPPH assay and results showed a dose-dependent radical scavenging potential and an IC of 24.23 {micro}g/mL, while antibacterial assay against S. aureus showed decent inhibition zones for the extract (5 - 7 mm) and the gel-patch (1 - 3.5 mm). In addition to invitro assays, in-silico analysis was carried out for predicting the effective usage of H. pluvialis against S. aureus strains. Conserved domain analysis identified the presence of a Cps2A domain of the LytR-CpsA-Psr (LCP) family in PTA. Physicochemical profiling revealed a hydrophilic, stable protein nature having high aliphatic index (85.07), low GRAVY score (-0.679), and a structured catalytic core with flanked disordered terminal regions. GC-MS analysis showed the presence of 15 compounds in the algal extract and ADMET analysis identified compounds with suitable drug-likeness, skin permeability and low systemic toxicity. The diversified residue-specific interactions for control drugs and the algal ligands in the conserved Cps2A domain favour a dual binding and synergistic therapeutic approach to target MRSA using the H. pluvialis-based gel-patch.