Potentiality of phytocompounds from Kalanchoe pinnata as an antibiofilm inhibitor of ESKAPE pathogens: A computational approach

The emergence of biofilm-associated antibiotic resistance among ESKAPE pathogens has become a significant global health concern. Nowadays, bioactive substances from plants can have a substantial impact on the development and spread of biofilms by interfering with various processes, including cell adhesion, quorum sensing, and the formation of extracellular polymeric substances (EPS). Through extensive in silico analysis, a set of phytocompounds was evaluated in this work for their anti-biofilm potential, toxicity, and drug-likeness characteristics. Single-molecule multiple-target theory was applied here. Among bioactive compounds, Bryotoxin-C appeared as the inhibitor compound, as it showed very high binding energies with each target protein of ESKAPE pathogens. It showed the highest binding energy, i.e., -11.1 Kcal/mol, with the clfB protein of Staphylococcus aureus. A molecular dynamics simulation analysis showing the stability of the bryotoxin-C-clfB bound complex across a 100 ns production run was used to further confirm the findings. Overall, this work shows how plant bioactive chemicals have environmentally benign inhibitory effects on ESKAPE viruses' ability to build biofilms. Additional drug discoveries will benefit from this study as well.