Dissecting the pathogenesis of SARS-CoV-2 Omicron and emerging variants

Professor Chu, Hin   (Principal Investigator (PI))

Professor Huang Jiandong   (Co-principal investigator)

Professor Yuen Kwok Yung   (Collaborator)

Dr Zhao Qian   (Co-Investigator)

Dr Shuai Huiping Vivian   (Co-principal investigator)

Professor Chan Jasper Fuk Woo   (Co-principal investigator)

Dr Li Cun   (Co-principal investigator)

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2023-06-01

6110000

Dissecting the pathogenesis of SARS-CoV-2 Omicron and emerging variants

1) SARS-CoV-2 2) Omicron 3) Pathogenesis 4) Infection 5) Replication

VirologyInfection/Parasitology

Biology and Medicine (M)

C7103-22G

Collaborative Research Fund (CRF) - Group Research Project 2022/2023

2022

On-going

1. Objective 1: Functional studies on Omicron spike substitutions for their contribution on virus entry, replication, and pathogenesis. 1.1. Functional characterization of individual Omicron spike substitutions for their contribution on virus entry. 1.2. Evaluate the entry of Omicron pseudoviruses in organoids. 1.3 Dissect the mechanism of the identified Omicron spike substitutions on virus entry. 1.4. Establish and characterize infectious clone of identified Omicron spike substitutions. 1.5. Investigate the pathogenicity of Omicron molecular clones in animal models. 2. Objective 2: Mechanistic studies on host protease usage for Omicron. 2.1. Identify and characterize additional host proteases that are important for Omicron entry. 2.2. Mechanistic investigations on how the identified host proteases facilitate Omicron entry. 2.3. Evaluate the antiviral activity of small molecule inhibitors against the identified proteases on Omicron replication and pathogenesis. 3. Objective 3:Comparative investigation of Omicron replication and the underlying mechanism in human lung and nasal epithelial cells. 3.1. Comparative characterization of Omicron replication in human lung and nasal epithelial cells. 3.2. Evaluate ACE2 usage during Omicron infection in nasal epithelial cells. 3.3. Investigate Omicron spike interaction partners in the nasal epithelial cells. 4. Objective 4: Further characterization of Omicron BA.2 and additional emerging variants on their replication characterization and pathogenicity. 4.1. Evaluate the replication and pathogenesis of Omicron BA.2 and additional emerging variants in vitro and in vivo. 4.2. Characterization of individual Omicron BA.2 spike substitutions for their contribution on virus entry. 4.3. Investigate the transmission and competition of Omicron BA.2 against Omicron BA.1 and/or other variants.