A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron <i>in vivo</i>

Daming Zuo; Yu Chen; Jian-piaoCai; Hao-Yang Yuan; Jun-Qi Wu; Yue Yin; Jing-Wen Xie; Jing-Min Lin; Jia Luo; Yang Feng; Long-Jiao Ge; Jia Zhou; Ronald J. Quinn; San-Jun Zhao; Xing Tong; Dong-Yan Jin; Shuofeng Yuan; Shao-Xing Dai; Min Xu

doi:10.1093/procel/pwac027

Volume 14 Issue 1

Jan. 2023

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Article Navigation > Protein&Cell > 2023 > 14(1): 37-50

Daming Zuo, Yu Chen, Jian-piaoCai, Hao-Yang Yuan, Jun-Qi Wu, Yue Yin, Jing-Wen Xie, Jing-Min Lin, Jia Luo, Yang Feng, Long-Jiao Ge, Jia Zhou, Ronald J. Quinn, San-Jun Zhao, Xing Tong, Dong-Yan Jin, Shuofeng Yuan, Shao-Xing Dai, Min Xu. A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo[J]. Protein&Cell, 2023, 14(1): 37-50. doi: 10.1093/procel/pwac027

Citation:

Daming Zuo, Yu Chen, Jian-piaoCai, Hao-Yang Yuan, Jun-Qi Wu, Yue Yin, Jing-Wen Xie, Jing-Min Lin, Jia Luo, Yang Feng, Long-Jiao Ge, Jia Zhou, Ronald J. Quinn, San-Jun Zhao, Xing Tong, Dong-Yan Jin, Shuofeng Yuan, Shao-Xing Dai, Min Xu. A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo[J]. Protein&Cell, 2023, 14(1): 37-50. doi: 10.1093/procel/pwac027

Citation:

Daming Zuo, Yu Chen, Jian-piaoCai, Hao-Yang Yuan, Jun-Qi Wu, Yue Yin, Jing-Wen Xie, Jing-Min Lin, Jia Luo, Yang Feng, Long-Jiao Ge, Jia Zhou, Ronald J. Quinn, San-Jun Zhao, Xing Tong, Dong-Yan Jin, Shuofeng Yuan, Shao-Xing Dai, Min Xu. A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo[J]. Protein&Cell, 2023, 14(1): 37-50. doi: 10.1093/procel/pwac027

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A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo

doi: 10.1093/procel/pwac027

1 Center for Pharmaceutical Sciences, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China;
2 Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China;
3 State Key Laboratory of Primate Biomedical Research;Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650500, China;
4 Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China;
5 Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China;
6 Griffith Institute for Drug Discovery, Griffith University, Brisbane 4111, Australia;
7 School of Life Sciences, Yunnan Normal University, Kunming 650500, China;
8 School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China;
9 Microbiome Medicine Center, Department of Laboratory medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510515, China

Received Date: 2022-05-25
Rev Recd Date: 2022-06-09
Publish Date: 2023-01-01

Abstract

Abstract

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
- hnRNPA2B1,
- PAC5,
- HBV,
- SARS-CoV-2 omicron,
- TBK1-IRF3 pathway,
- type I IFNs

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References(44)

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