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

Autor: Daming Zuo, Yu Chen, Jian-piao Cai, 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
Rok vydání: 2022
Předmět:
Zdroj: Protein & Cell.
ISSN: 1674-8018
1674-800X
Popis: 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.
Databáze: OpenAIRE
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