Unraveling the novel role of casein kinase II in Zika virus infection using a quantitative phosphoproteomics approach

Dr Chan, Jasper Fuk Woo   (Principal Investigator (PI))

Professor Yuen Kwok Yung   (Co-Investigator)

Dr Yuan Shuofeng   (Co-Investigator)

Dr Sze Kong Hung   (Co-Investigator)

Dr Chu Hin   (Co-Investigator)

36

2019-09-01

2022-08-31

982013

Unraveling the novel role of casein kinase II in Zika virus infection using a quantitative phosphoproteomics approach

antiviral, casein kinase, phosphoproteomics, virus, Zika

Infection/ParasitologyClinical Microbiology

Biology and Medicine (M)

17123319

General Research Fund (GRF)

2019

Completed

1 Objective 1: To investigate the role of CK2 in ZIKV infection. Extending from our identification of CK2 as the most activated kinase in ZIKV-infected glial cells which affects virus replication, we will detailedly investigate its role in ZIKV infection in Objective 1. -Objective 1.1: To understand the biology of CK2 upon ZIKV infection: how the expression/activation of CK2 is modulated by ZIKV, cellular distribution of CK2 in ZIKV-infected cells, and the effect of CK2 overexpression on ZIKV replication. -Objective 1.2: To characterize the function of CK2 in ZIKV infection: CK2’s effects on multiple ZIKV strains in different cell types including human neural progenitor cells. -Objective 1.3: To dissect the mechanism of how CK2 affects ZIKV replication: the step(s) of the ZIKV replication cycle CK2 is involved in. 2 Objective 2: To evaluate the effects of CK2 inhibitors as novel treatment options for ZIKV infection. Our preliminary data showed that the CK2 inhibitor, silmitasertib, has in-vitro and in-vivo anti-ZIKV effects. In Objective 2, we will validate this finding and thoroughly assess the anti-ZIKV effects of silmitasertib and other CK2 inhibitors using a lethal mouse model (survival) and additionally a pregnant mouse model (vertical transmission). In particular, we will detailedly investigate the anti-ZIKV effects of CK2 inhibitors on neurogenesis and testicular damage. -Objective 2.1: To investigate the in-vitro anti-ZIKV activity of CK2 inhibitors: to select the drugs with the best in-vitro anti-ZIKV properties for in-vivo evaluation. -Objective 2.2: To assess the in-vivo anti-ZIKV activity of CK2 inhibitors: in lethal and pregnant mouse models, and study the effects of CK2 inhibitors in reverting ZIKV-associated disruption in neurogenesis, testicular damage, and apoptosis.