A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo
Protein & Cell
; (12): 37-50, 2023.
Artigo
em Inglês
| WPRIM (Pacífico Ocidental)
| ID: wpr-971609
Biblioteca responsável:
WPRO
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.
Texto completo:
Disponível
Contexto em Saúde:
ODS3 - Meta 3.3 Acabar com as doenças tropicais negligenciadas e combater as doenças transmissíveis
Problema de saúde:
Pneumonía
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Antivirais
/
Interferon Tipo I
/
Vírus da Hepatite B
/
Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B
/
SARS-CoV-2
/
COVID-19
Limite:
Animais
Idioma:
Inglês
Revista:
Protein & Cell
Ano de publicação:
2023
Tipo de documento:
Artigo