Implications of virtual screening for South African natural compounds against Plesiomonas shigelloides, a pathogen...

Plesiomonas shigelloides is an emerging pathogen associated with gastroenteritis and poses a growing public health concern, especially in regions with limited access to advanced medical treatments. The purpose of this study was to explore the therapeutic potential of South African natural product compounds against P. shigelloides by targeting the essential enzyme Pyridoxine 5'-phosphate synthase or PPS (encoded by PdxJ). P. shigelloides proteomes (n = 26) were processed using the Bacterial Pan Genome Analysis (BPGA) pipeline to identify conserved targets. Targeting conserved protein ensures the potential for broad-spectrum efficacy. PPS was chosen as drug target and its structure was predicted using AlphaFold, enabling high-confidence modeling. Subsequently, docking was performed using AutoDock Vina, focusing on a library of South African compounds (n > 1000). The three inhibitors demonstrating strong binding affinities to the PPS were Scutiaquinone A, Mesquitol-(4α→5)-3,3',4',7,8-pentahydroxyflavonone, and Riccardin C. To further validate the stability and efficacy of these interactions, molecular dynamics (MD) simulations were carried out for 100 ns. The simulations revealed stable interactions between the inhibitors and PPS, suggesting potential inhibition of the PPS enzyme. Mesquitol derivative was found to be the safest and recommended for further experimental validation. This study highlights the promising potential of South African natural compounds in combating P. shigelloides infections, paving the way for the development of novel therapeutic strategies.