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Chelerythrine as an anti-Zika virus agent: therapeutic potential and mode of action

Erica Españo, Jiyeon Kim, Chong-Kil Lee, Robert G. Webster, Richard J. Webby, Jeong-Ki Kim
doi: https://doi.org/10.1101/2022.12.16.520682
Erica Españo
1Department of Pharmacy, Korea University College of Pharmacy, Sejong 30019, Republic of Korea
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Jiyeon Kim
1Department of Pharmacy, Korea University College of Pharmacy, Sejong 30019, Republic of Korea
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Chong-Kil Lee
2Department of Pharmaceutics, College of Pharmacy, Chungbuk National University, Cheongju 28644, Republic of Korea
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Robert G. Webster
3Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38195, USA
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Richard J. Webby
3Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38195, USA
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Jeong-Ki Kim
1Department of Pharmacy, Korea University College of Pharmacy, Sejong 30019, Republic of Korea
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  • For correspondence: jkfrancis@korea.ac.kr
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Abstract

Zika virus (ZIKV) is a mosquito-borne virus that has been associated with adult and neonatal neurological conditions. So far, there is no approved drug or vaccine against ZIKV infection; thus, ZIKV remains a global health threat. Here, we explored the effects of chelerythrine (CTC), a known protein kinase C (PKC) inhibitor, against ZIKV infection in cell culture models to determine its potential as a therapeutic agent for ZIKV infection. We found that CTC protected Vero cells from ZIKV-induced cytopathic effects in a dose-dependent manner. It also reduced the production of ZIKV in Vero and A549 cells. In contrast, other PKC inhibitors failed to protect Vero cells from ZIKV-induced cytopathic effects, indicating PKC-independent mechanisms underlying the effects of CTC on ZIKV. Further investigation suggested that CTC inhibited ZIKV attachment/binding rather than internalization in the host cells. Pretreatment of cell-free ZIKV particles rather than pretreatment of cells with CTC resulted in reduced ZIKV infectivity in vitro, indicating that CTC blocked the attachment/binding of the ZIKV particles to host factors. In silico analyses suggested that these effects are potentially due to the binding of CTC to the ZIKV E protein, which may occlude the interaction of the E protein with attachment factors or receptors on the host cell surface. Overall, our findings suggest that CTC reduces the infectivity of ZIKV particles through PKC- and cell-independent mechanisms. Our findings also support further exploration of CTC as an anti-ZIKV agent.

Competing Interest Statement

The authors have declared no competing interest.

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Posted December 19, 2022.
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Chelerythrine as an anti-Zika virus agent: therapeutic potential and mode of action
Erica Españo, Jiyeon Kim, Chong-Kil Lee, Robert G. Webster, Richard J. Webby, Jeong-Ki Kim
bioRxiv 2022.12.16.520682; doi: https://doi.org/10.1101/2022.12.16.520682
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Chelerythrine as an anti-Zika virus agent: therapeutic potential and mode of action
Erica Españo, Jiyeon Kim, Chong-Kil Lee, Robert G. Webster, Richard J. Webby, Jeong-Ki Kim
bioRxiv 2022.12.16.520682; doi: https://doi.org/10.1101/2022.12.16.520682

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