Abstract
BACKGROUND: Xanthomonas oryzae pv. oryzae is a plant pathogen responsible for causing one of the most severe bacterial diseases in rice, known as bacterial leaf blight that poses a major threat to global rice production. Even though several experimental compounds and chemical agents have been tested against X. oryzae pv. oryzae, still no approved drug is available. In this study, a subtractive genomic approach was used to identify potential therapeutic targets and repurposible drug candidates that could control of bacterial leaf blight in rice plants. RESULTS: The entire proteome of the pathogen underwent an extensive filtering process which involved removal of the paralogous proteins, rice homologs, non-essential proteins. Out of the 4382 proteins present in Xoo proteome, five hub proteins such as dnaA, dnaN, recJ, ruvA, and recR were identified for the druggability analysis. This analysis led to the identification of dnaN-encoded Beta sliding clamp protein as a potential therapeutic target and one experimental drug named [(5R)-5-(2,3-dibromo-5-ethoxy-4hydroxybenzyl)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid that can be repurposed against it. Molecular docking and 100 ns long molecular dynamics simulation suggested that the drug can form stable complexes with the target protein over time. CONCLUSION: Findings from our study indicated that the proposed drug showed potential effectiveness against bacterial leaf blight in rice caused by X. oryzae pv. oryzae. It is essential to keep in consideration that the procedure for developing novel drugs can be challenging and complicated. Even the most promising results from in silico studies should be validated through further in vitro and in vivo investigation before approval.