Common metabolic pathway harnessed by multiple emerging human viruses as potential broad spectrum antiviral target
Grant Data
Project Title
Common metabolic pathway harnessed by multiple emerging human viruses as potential broad spectrum antiviral target
Principal Investigator
Professor Yuen, Kwok Yung
(Principal Investigator (PI))
Co-Investigator(s)
Professor Yuan Shuofeng
(Co-Investigator)
Professor Chu Hin
(Co-Investigator)
Duration
36
Start Date
2020-01-01
Completion Date
2022-12-31
Amount
1114728
Conference Title
Common metabolic pathway harnessed by multiple emerging human viruses as potential broad spectrum antiviral target
Keywords
broad-spetrum, drug target, emerging human viruses, lipid metabolism, SREBPs
Discipline
Infection/ParasitologyDiabetes/Metabolism
Panel
Biology and Medicine (M)
HKU Project Code
17126919
Grant Type
General Research Fund (GRF)
Funding Year
2019
Status
Completed
Objectives
1 Activation of SREBP by viruses: 1.1. Documenting the up-regulation of lipogenesis pathways in virus-infected cell cultures and tissues of virus-infected mouse models. Three virus species with distinct characteristics will be involved, including MERS-CoV, EV-A71 and ZIKV. 1.2. Identification and characterization of viral proteins that activate SREBP-mediated lipogenesis of each virus. 2 Mechanism of SREBP activation: 2.1. Determination and characterization of proteolytic cleavage activity of the selected viral proteins against precursor SREBP. 2.2. Investigation of the ER-stress-induced SREBP1/2 activation that is bridged by Caspase 2 functionality. 3 Effect of blockade on SREBP activation: 3.1. Effect on virus replication of MERS-CoV, EV-A71 and ZIKV in cell cultures by using RNAi technology and pharmaceutical inhibitors. 3.2. Effect on virus replication of MERS-CoV and ZIKV in lethal mouse models.