SARS-CoV-2 nsp13 restricts episomal DNA transcription and hepatitis B virus infection

Non-structural protein 13 (nsp13), as the helicase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been shown to own multiple functions. Here, we reported that nsp13 could restrict episomal DNA transcription without affecting chromosomal DNA. By using different truncated and mutant forms of nsp13, we demonstrated that its NTPase and helicase activities contributed to episomal DNA transcriptional inhibition. This restriction required direct interaction with episomal DNA. By screening nsp13 interacting proteins, we found that structural maintenance of chromosomes 4 was involved. Given the fact that the episomal DNA of hepatitis B virus (HBV) is the major obstacle for antiviral treatment, we investigated and revealed that nsp13 could significantly restrict HBV replication in vitro and in vivo. In conclusion, our findings demonstrated that SARS-CoV-2 nsp13 can specifically inhibit episomal DNA transcription and can be served as a potential antiviral for HBV infection. HEK293T cells were co-transfected with pEF1α-Luc and pHA-NSP13，pHA-NSP13 D374A mutant or empty vector for 24 h, chromosomal gene expression was determined by RNA-seq. This experiment to detect the effect of SARS-CoV-2 NSP13 onchromosomal gene expression.