PolyU ABCT Prof. Ko uncovered the key mechanism underlying the antiviral and neuroprotective effects of tetrandrine
Researchers from The Hong Kong Polytechnic University (PolyU) have uncovered the key mechanism underlying the antiviral and neuroprotective effects of tetrandrine, a compound extracted from the root of the traditional Chinese medicine Stephania tetrandra. Previously known for its ability to block Ebola virus infection, tetrandrine’s exact cellular target had remained elusive. The PolyU team, led by Professor Ben Ko Chi-bun of the Department of Applied Biology and Chemical Technology, used an advanced photoaffinity probe technique and multi-omics analysis to visualize tetrandrine’s interactions within cells. They discovered that tetrandrine does not directly inhibit calcium channels, as previously assumed. Instead, it binds to the lysosomal integral membrane protein type-2 (LIMP-2) located on lysosomes—crucial organelles responsible for metabolism and waste processing. By attaching to LIMP-2, tetrandrine blocks the release of sphingosine, a lipid molecule required for calcium signalling. Diminished sphingosine levels subsequently reduce calcium entry into cells, thereby influencing vital biological processes such as immune response, metabolism, neuronal function, and viral replication.
This discovery provides a new mechanistic explanation for tetrandrine’s antiviral, anti-inflammatory, and anticancer properties. The compound’s ability to target LIMP-2 and regulate lysosomal calcium release could disrupt the survival and replication mechanisms of deadly viruses like Ebola and COVID-19. Moreover, the identification of LIMP-2 as a regulator of calcium signalling opens up a new frontier in drug discovery, especially for conditions driven by calcium imbalance. These include neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease, as well as certain metastatic cancers.
According to Professor Ko, this is the first study to uncover a functional role of LIMP-2 in calcium signalling, revealing an entirely new pathway for nicotinic acid adenine dinucleotide phosphate (NAADP)-regulated calcium signalling mediated through LIMP-2 and sphingosine. From both a cell biology and therapeutic perspective, these findings represent a breakthrough, identifying a critical molecular target for novel antiviral and neuroprotective therapies. The PolyU team’s integrated technology platform enables the comprehensive study of natural compounds and their molecular targets, paving the way for innovative drug development. This research demonstrates how modern analytical approaches can revitalize traditional Chinese medicine by translating its natural products into scientifically validated therapeutic agents. The findings were published in Nature Communications under the title “Tetrandrine regulates NAADP-mediated calcium signaling through a LIMP-2-dependent and sphingosine-mediated mechanism.”
