SARS-CoV-2 nsp13 suppresses hepatitis B virus replication by targeting cccDNA transcription.

SARS-CoV-2 nsp13 suppresses hepatitis B virus replication by targeting cccDNA transcription.

Publication date: Oct 07, 2024

SARS-CoV-2 nonstructural protein 13 (nsp13) has been shown to selectively suppress the transcription of episomal DNA while sparing chromosomal DNA. Hepatitis B Virus (HBV) harbors covalently closed circular DNA (cccDNA), a form of viral episomal DNA found within infected hepatocyte nuclei. The persistence of cccDNA is the major cause of chronic HBV infection. In this study, we investigated the impact of SARS-CoV-2 nsp13 on HBV replication, particularly in the context of cccDNA. Our findings demonstrate that nsp13 effectively hinders HBV replication by suppressing the transcription of HBV cccDNA, both in vitro and in vivo. Additionally, we observed that SARS-CoV-2 nsp13 binds to HBV cccDNA and its NTPase and helicase activities contribute significantly to inhibiting HBV replication. Furthermore, our screening identified the interaction between nsp13 and structural maintenance of chromosomes 4, opening new avenues for future mechanistic inquiries. This study presents the evidence suggesting the potential utilization of SARS-CoV-2 nsp13 as a strategy to impede HBV replication by specifically targeting cccDNA. These findings provide a proof of concept for exploring nsp13 as a prospective approach in combating HBV infection. To effectively combat hepatitis B virus (HBV), it is imperative to develop potent antiviral medications targeting covalently closed circular DNA (cccDNA). Our investigation aimed to assess the impact of SARS-CoV-2 nsp13 on HBV replication across diverse HBV models, confirming its ability to significantly reduce several HBV replication markers. Additionally, our identification of the interaction between nsp13 and SMC4 opens the door for further mechanistic exploration. This marks a paradigm shift in our approach to HBV antiviral therapy, introducing an entirely novel perspective. Our findings propose a novel strategy for developing anti-HBV drugs that specifically target HBV cccDNA.

Concepts Keywords
Dna cccDNA
Hepatitis hepatitis B virus
Nsp13 nsp13
Sparing transcriptional repression
Vitro

Semantics

Type Source Name
disease IDO replication
disease IDO protein
disease MESH infection
disease MESH repression

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