The identification of novel TCM compounds and its mechanism of action against SARS-CoV-2 infection
The recent pandemic of COVID-19 caused by the SARS-CoV-2 virus is ongoing and causing serious global health burden and high socioeconomic impact in the world. However, the speed of transmission outpaced research in vaccine and drug development even though much efforts being made. As postulated by various studies, COVID-19 may become an endemic virus in the coming years when the waves of outbreak subside. Therefore, identification of effective drugs against the virus becomes particularly important. Based on our strength in TCM combined with the experience of the PI in virology and immunology research, a study should be conducted in HKBU to develop new anti-SARS-CoV-2 drugs. Others have used computational modelling or re-purposing of approved clinical drugs to predict and test against the virus. However, it may be useful in the short run with speed, but they may not specifically target the viral proteins per se. Therefore, this proposed study sought to develop a high throughput biological system to screen TCM compounds that show inhibitory activities against SARS-CoV-2 infection in human lung epithelial and alveolar cells. We foresee at least 1000 compounds will be screened to obtain a handful of compounds showing inhibition. The ones with highest potency will be used to understand the mechanism of action. Additional experiments will be performed to evaluate the biological functions and the chemical structure of these inhibitors. The biological inhibition will be important to determine not only the compounds that inhibit viral entry, and also if certain pathways favour SARS-CoV-2 infection and inhibiting these pathways could impede viral replication. Likewise, the chemical structure of the inhibitors and how they bind physically can be determined by co-crystallisation, which will provide accurate information for optimisation for drug development. Ultimately, we aim to identify novel TCM compounds against SARS-CoV-2 in the ongoing fight against pandemic COVID-19 and hope to contribute as a team from HKBU. The PhD candidate recruited through this scheme can learn about molecular biology, immunology, virology, TCM, and structural biology, and he/she will be trained as a strong interdisciplinary researcher in the future.
The student is required to perform biological experiments using cell and virus culture for screening the TCM compounds for inhibitory activities, and have background knowledge of chemical structures of the TCM and protein structures.