1. Heterogeneous nuclear ribonucleoprotein A2B1, a novel drug target for hepatitis B virus infection
- Author
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Jun-Qi Wu, Min Xu, Yu Chen, Jingmin Lin, Hao Chen, Daming Zuo, Shao-Xing Dai, Hao-Yan Yuan, Jia-Yao Xiang, Ronald Quinn, Cheng Xiang, San-Jun Zhao, Yue-Hai Shen, Jia Luo, Yue Yin, Hai-Zhou Li, Long-Jiao Ge, Ya-Ming Li, and Yang Feng
- Subjects
Hepatitis B virus ,Heterogeneous nuclear ribonucleoprotein ,Drug target ,medicine ,Biology ,medicine.disease_cause ,Virology - Abstract
HBV infection is a major global health burden that needs novel immunotherapeutic approaches. Herein, we show that heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is a novel drug target for HBV infection. We reveal the new target with highly selective probes of PAC5, a natural sesquiterpene derivative. PAC5 show potent anti-HBV activity in vivo and in vitro. Further studies on its mode of action indicate that PAC5 binds to the residue Asp49 and a deep groove in the RNA recognition motif1 (RRM1) region of hnRNPA2B1. PAC5-bound hnRNPA2B1 is activated, dimerized, and translocated to the cytoplasm where it activates the TBK1-IRF3 pathway, leading to the production of type I interferons (IFNs). Furthermore, PAC5 also suppresses other viral replications, such as SARS-CoV-2 and vesicular stomatitis virus (VSV). Our results indicate that PAC5 is the first small molecule agonist of hnRNPA2B1, a drug target potentially valid for broad-spectrum viral infections, providing a novel strategy for viral immunotherapy.
- Published
- 2021