Identification of neprilysin as a potential target of arteannuin using computational drug repositioning

ABSTRACT The discovery of arteannuin (qinghaosu) in the 20th Century was a major advance for medicine. Besides functioning as a malaria therapy, arteannuin is a pharmacological agent in a range of other diseases, but its mechanism of action remains obscure. In this study, the reverse docking server PharmMapper was used to identify potential targets of arteannuin. The results were checked using the chemical-protein interactome servers DRAR-CPI and DDI-CPI, and verified by AutoDock Vina. The results showed that neprilysin (also known as CD10), a common acute lymphoblastic leukaemia antigen, was the top disease-related target of arteannuin. The chemical-protein interactome and docking results agreed with those of PharmMapper, further implicating neprilysin as a potential target. Although experimental verification is required, this study provides guidance for future pharmacological investigations into novel clinical applications for arteannuin.

Identification of a Potential Target of Capsaicin by Computational Target Fishing.

Capsaicin, the component responsible for the pungency of chili peppers, shows beneficial effects in many diseases, although the underlying mechanisms remain unclear. In the present study, the potential targets of capsaicin were predicted using PharmMapper and confirmed via chemical-protein interactome (CPI) and molecular docking. Carbonic anhydrase 2 was identified as the main disease-related target, with the pharmacophore model matching well with the molecular features of capsaicin. The relation was confirmed by CPI and molecular docking and supported by previous research showing that capsaicin is a potent inhibitor of carbonic anhydrase isoenzymes. The present study provides a basis for understanding the mechanisms of action of capsaicin or those of other natural compounds.