Search for novel anti-fungal compounds targeting cytochrome of Fusarium circinatum by virtual screening

摘要

Fusarium circinatum is a disease-causing fungal agent responsible for pitch canker disease in pine trees. In this study, the cytochrome b protein which plays an important role in electron transport chain for respiration is taken as a crucial target for developing anti-fungal inhibitors. We predicted the protein model of cytochrome b in Fusarium circinatum based on the Saccharomyces cytochrome b template. The A-chain of cytochrome b in Fusarium circinatum is identical to the N-chain of cytochrome b of Saccharomyces cerevisiae. The modeled cytochrome b structure was used to screen ZINC database compounds through DOCKBlaster which yielded 200 top scoring compounds. We report the top two compounds namely, ZINC53798 and ZINC18029019 which can be further evaluated for their anti-fungal activities through experimental means. The binding affinity scores for these two are -37.75 and -37.09 kcal/mol respectively. They are expected to inhibit the function of cytochrome b at the ubiquinol binding site due to good binding affinity. This inhibition in turn will render inactivity to Fusarium cytochrome b by preventing binding of ubiquinol thus, hindering the metabolic process. The mode of action can be further elucidated and prove the potential of using these compounds as anti-fungal agents.