ArticleAntimicrobial agents and chemotherapy2020
The Dihydroquinolizinone Compound RG7834 Inhibits the Polyadenylase Function of PAPD5 and PAPD7 and Accelerates the Degradation of Matured Hepatitis B Virus Surface Protein mRNA.
Article in Antimicrobial agents and chemotherapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- The Post-Transcriptional Regulatory Element of Hepatitis B Virus: From Discovery to Therapy.Viruses · 2024Pooled it
- Safety, pharmacokinetics, and pharmacodynamics of the antisense oligonucleotide RO7239958 in healthy volunteers and adults with chronic hepatitis B infection.Antimicrobial agents and chemotherapy · 2025Trial
- Safety, Tolerability, and Pharmacokinetics of the Novel Hepatitis B Virus Expression Inhibitor GST-HG131 in Healthy Chinese Subjects: a First-in-Human Single- and Multiple-Dose Escalation Trial.Antimicrobial agents and chemotherapy · 2022Trial
- A visible assay for evaluating the inhibitory activity of drug and antibody against HBV infection.Microbiology spectrum · 2026Article
- A hepatitis B virus RNA-sensing and RNA-editing-dependent reporter system.Journal of virology · 2025Article
- Noncanonical Poly(A) Polymerase TENT4 Drives Expression of Subgenomic Hepatitis A Virus RNAs in Infected Cells.Viruses · 2025Article
- Hepato-selective dihydroquinolizinones active against hepatitis A virus in vitro and in vivo.Antiviral research · 2025Article
- Dual Roles of Host Zinc Finger Proteins in Viral RNA Regulation: Decay or Stabilization.International journal of molecular sciences · 2024Review
- An allosteric inhibitor of sirtuin 2 blocks hepatitis B virus covalently closed circular DNA establishment and its transcriptional activity.Antiviral research · 2024Article
- "PROTAC" modified dihydroquinolizinones (DHQs) that cause degradation of PAPD-5 and inhibition of hepatitis A virus and hepatitis B virus, in vitro.Bioorganic & medicinal chemistry letters · 2024Article
- Article
- Pregenomic RNA Launch Hepatitis B Virus Replication System Facilitates the Mechanistic Study of Antiviral Agents and Drug-Resistant Variants on Covalently Closed Circular DNA Synthesis.Journal of virology · 2022Article
- The landscape of the long non-coding RNAs and circular RNAs of the abdominal fat tissues in the chicken lines divergently selected for fatness.BMC genomics · 2022Article
- The ZCCHC14/TENT4 complex is required for hepatitis A virus RNA synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Host Poly(A) Polymerases PAPD5 and PAPD7 Provide Two Layers of Protection That Ensure the Integrity and Stability of Hepatitis B Virus RNA.Journal of virology · 2021Article
- Hepatoselective Dihydroquinolizinone Bis-acids for HBsAg mRNA Degradation.ACS medicinal chemistry letters · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis B virus (HBV) mRNA metabolism is dependent upon host proteins PAPD5 and PAPD7 (PAPD5/7). PAPD5/7 are cellular, noncanonical, poly(A) polymerases (PAPs) whose main function is to oligoadenylate the 3' end of noncoding RNA (ncRNA) for exosome degradation. HBV seems to exploit these two ncRNA quality-control factors for viral mRNA stabilization, rather than degradation. RG7834 is a small-molecule compound that binds PAPD5/7 and inhibits HBV gene production in both tissue culture and animal study. We reported that RG7834 was able to destabilize multiple HBV mRNA species, ranging from the 3.5-kb pregenomic/precore mRNAs to the 2.4/2.1-kb hepatitis B virus surface protein (HBs) mRNAs, except for the smallest 0.7-kb X protein (HBx) mRNA. Compound-induced HBV mRNA destabilization was initiated by a shortening of the poly(A) tail, followed by an accelerated degradation process in both the nucleus and cytoplasm. In cells expressing HBV mRNA, both PAPD5/7 were found to be physically associated with the viral RNA, and the polyadenylating activities of PAPD5/7 were susceptible to RG7834 repression in a biochemical assay. Moreover, in PAPD5/7 double-knockout cells, viral transcripts with a regular length of the poly(A) sequence could be initially synthesized but became shortened in hours, suggesting that participation of PAPD5/7 in RNA 3' end processing, either during adenosine oligomerization or afterward, is crucial for RNA stabilization.
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