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A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo.
- Source :
- Protein & Cell; Jan2023, Vol. 14 Issue 1, p37-50, 14p
- Publication Year :
- 2023
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 1674800X
- Volume :
- 14
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Protein & Cell
- Publication Type :
- Academic Journal
- Accession number :
- 163120119
- Full Text :
- https://doi.org/10.1093/procel/pwac027