Host PFKFB3-dependent glycolytic reprogramming as a broad-spectrum antiviral strategy

Dr Yuan, Shuofeng   (Principal Investigator (PI))

Professor Sun Hongzhe   (Co-Investigator)

Dr Lam Jenny Ka Wing   (Co-Investigator)

36

2021-11-01

1475920

Host PFKFB3-dependent glycolytic reprogramming as a broad-spectrum antiviral strategy

antiviral, broad-spectrum, Glycolysis, host-virus interaction, mouse model, PFKFB3

Others - Medicine, Dentistry and Health

20190732

Health and Medical Research Fund - Full Grant

2020

On-going

i.objectives: the current therapeutic arsenal against viral infections remains poor, with limited spectrum of coverage and appears inadequate to face the emergence of pandemic and antiviral resistance. This study aims to develop a broad-spectrum antiviral strategy for rapid epidemic control and early treatment with better clinical outcome. ii. hypothesis to be tested: we performed metabolomics on the virus–infected human primary cells, based on which we hypothesized that host PFKFB3-dependent glycolysis pathway with broad-relevance to multiple virus replications and might be a vulnerable host target for antiviral intervention. iii.design and subjects: two virus species with distinct characteristics will be involved, including influenza A H1N1 and SARS-CoV-2. (a) We will document the perturbation of glycolysis pathways in virus-infected primary cell cultures and animal tissues as well as to pinpoint which viral protein(s) that activate/suppress the PFKFB3-dependent glycolysis. (b) We will determine the effect on blockade of virus-induced and PFKFB3-dependent glycolysis using pharmacological inhibitors and gene manipulations in vitro and in vivo. iv. instruments: NA v. interventions: NA vi. main outcome measures: EC50, CC50, LD50 as measured in cell lines and mouse models. vii. data analysis: NA viii. expected results: we will (a) document the commonly altered glucose metabolic genes after different virus infections; (b) elucidate the mechanism of action how virus manipulate the genes’ expressions and functionalities; (c) evaluate the potency and bioavailability of the identified compound in vitro and in vivo; (d) determine the in vitro and in vivo outcome of infection after PFKFB3 gene knockout.