biostudies-literatureUnknown15(9)Tian KNumerous viral outbreaks have threatened us throughout history. Here, we demonstrated a nucleic acid-based antiviral strategy named AntiV-SGN. Unlike those CRISPR-mediated methods, AntiV-SGN has advantages of no targets' sequence limitation, such as protospacer adjacent motif (PAM) or protospacer flanking sequence (PFS), being universal for both DNA and RNA viruses. AntiV-SGN was composed of a FEN1 protein and specific hpDNAs targeting viruses' nucleic acid. Its antiviral ability was tested on SARS-CoV-2 and HBV respectively. Reporter assays in human cells first illustrated the feasibility of AntiV-SGN. Then, it was verified that AntiV-SGN destroyed about 50% of live RNAs of SARS-CoV-2 in Vero cells and 90% cccDNA of HBV in HepG2.2.15 cells. It was also able to remove viral DNA integrated Microbial biotechnology2488-2501https://www.ebi.ac.uk/biostudies/studies/S-EPMC9437879biostudies-literatureAntiV-SGN: a universal antiviral strategy to combat both RNA and DNA viruses by destroying their nucleic acids without sequence limitation.PMC9437879Tian KLiu YWang PQi ZZhu FXu SQiang HZhou GChi YGuo QfalseAntiV-SGN: a universal antiviral strategy to combat both RNA and DNA viruses by destroying their nucleic acids without sequence limitation.Numerous viral outbreaks have threatened us throughout history. Here, we demonstrated a nucleic acid-based antiviral strategy named AntiV-SGN. Unlike those CRISPR-mediated methods, AntiV-SGN has advantages of no targets' sequence limitation, such as protospacer adjacent motif (PAM) or protospacer flanking sequence (PFS), being universal for both DNA and RNA viruses. AntiV-SGN was composed of a FEN1 protein and specific hpDNAs targeting viruses' nucleic acid. Its antiviral ability was tested on SARS-CoV-2 and HBV respectively. Reporter assays in human cells first illustrated the feasibility of AntiV-SGN. Then, it was verified that AntiV-SGN destroyed about 50% of live RNAs of SARS-CoV-2 in Vero cells and 90% cccDNA of HBV in HepG2.2.15 cells. It was also able to remove viral DNA integrated 2022-01-01T00:00:00Z2022 Sep2025-04-18T22:42:22.657Z2025-04-07T10:29:38.501ZS-EPMC94378793561187410.1111/1751-7915.14076