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A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo.
Zuo, Daming; Chen, Yu; Cai, Jian-Piao; Yuan, Hao-Yang; Wu, Jun-Qi; Yin, Yue; Xie, Jing-Wen; Lin, Jing-Min; Luo, Jia; Feng, Yang; Ge, Long-Jiao; Zhou, Jia; Quinn, Ronald J; Zhao, San-Jun; Tong, Xing; Jin, Dong-Yan; Yuan, Shuofeng; Dai, Shao-Xing; Xu, Min.
  • Zuo D; Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China.
  • Chen Y; Microbiome Medicine Center, Department of Laboratory medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Cai JP; Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China.
  • Yuan HY; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China.
  • Wu JQ; Center for Pharmaceutical Sciences, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
  • Yin Y; Center for Pharmaceutical Sciences, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
  • Xie JW; Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China.
  • Lin JM; Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China.
  • Luo J; Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China.
  • Feng Y; Center for Pharmaceutical Sciences, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
  • Ge LJ; Center for Pharmaceutical Sciences, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
  • Zhou J; State Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650500, China.
  • Quinn RJ; Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
  • Zhao SJ; Griffith Institute for Drug Discovery, Griffith University, Brisbane 4111, Australia.
  • Tong X; School of Life Sciences, Yunnan Normal University, Kunming 650500, China.
  • Jin DY; State Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650500, China.
  • Yuan S; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China.
  • Dai SX; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China.
  • Xu M; State Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650500, China.
Protein Cell ; 14(1): 37-50, 2023 01.
Article in English | MEDLINE | ID: covidwho-2222720
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Hepatitis B virus / Heterogeneous-Nuclear Ribonucleoprotein Group A-B / SARS-CoV-2 Type of study: Experimental Studies Topics: Variants Limits: Animals Language: English Journal: Protein Cell Journal subject: Biochemistry Year: 2023 Document Type: Article Affiliation country: Procel

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Hepatitis B virus / Heterogeneous-Nuclear Ribonucleoprotein Group A-B / SARS-CoV-2 Type of study: Experimental Studies Topics: Variants Limits: Animals Language: English Journal: Protein Cell Journal subject: Biochemistry Year: 2023 Document Type: Article Affiliation country: Procel