Proteome-Wide Mapping of Artesunate Targets Reveals Enrichment of the Ubiquitin-Proteasome System

Artesunate (AS) has great pharmacokinetic and clinical value. However, a comprehensive and up-to-date study exclusively focusing on AS direct binding proteins has not yet been conducted.

We performed a systematic, data-driven mapping of AS-binding protein via HuProt™ 20K human proteome microarray. To characterize the biological features of AS-binding proteins through a series of bioinformatic analyses.

Firstly, AS targeted ubiquitin-mediated proteolysis, mineral absorption, Salmonella infection and glycolysis/gluconeogenesis. Among them, ubiquitin-mediated proteolysis has highest confidence scores, chaperone complex and ubiquitin-like protein conjugating enzyme activity were enriched in this set. Secondly, we showed that the bioactivity of AS encompasses a multifaceted range of health-promoting effects. Collectively, this study provided a valuable resource for AS-binding proteins. Furthermore, protein biological function is determined by their three-dimensional structure, when a protein fails to fold into its native structure, the proteins undergo mislocalisation/abnormal accumulation/degradation, leading to conformational diseases (CDs).

Considering that AS could target ubiquitin-proteasome system (UPS) and encompass a multifaceted range of health-promoting effects, a comprehensive understanding of the regulatory effects of AS on the UPS and its intrinsic mechanisms will enhance its ability to serve as a protective agent to fight against CDs.