The Dihydroquinolizinone Compound RG7834 Inhibits the Polyadenylase Function of PAPD5 and PAPD7 and Accelerates the Degradation of Matured Hepatitis B Virus Surface Protein mRNA-Reference-Cited by-同舟云学术

The Dihydroquinolizinone Compound RG7834 Inhibits the Polyadenylase Function of PAPD5 and PAPD7 and Accelerates the Degradation of Matured Hepatitis B Virus Surface Protein mRNA

Published:2020-12-16 Issue:1 Volume:65 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Sun Liren¹,Zhang Fang¹,Guo Fang²,Liu Fei²,Kulsuptrakul Jessie³,Puschnik Andreas³,Gao Min²,Rijnbrand Rene²,Sofia Michael²,Block Timothy¹,Zhou Tianlun¹^ORCID

Affiliation:

1. Baruch S. Blumberg Institute, Department of Translational Medicine, Doylestown, Pennsylvania, USA

2. Arbutus BioPharma, Warminster, Pennsylvania, USA

3. Chan Zuckerberg Biohub, San Francisco, California, USA

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.

Funder

The Commonwealth of Pennsylvania

Hepatitis B Foundation

Arbutus BioPharma

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/AAC.00640-20

Reference55 articles.

1. Drugs in Development for Hepatitis B