A novel antiviral peptide Laby A1/A3 precursor-SUMO against PCV2 replication with broad-spectrum antiviral potential

Porcine circovirus type 2 (PCV2), the etiological agent of porcine circovirus-associated diseases (PCVAD), causes significant economic losses in swine production. In this study, the Labyrinthopeptin A1/A3 precursor-SUMO fusion (Laby A1/A3 precursor-SUMO), a novel therapeutic antiviral peptide, was successfully expressed and purified. The Laby A1/A3 precursor-SUMO was effective against PCV2 replication in the PK-15 cells in a concentration-dependent manner, as evidenced by significantly reduced viral Cap protein expression and DNA copy number. Notably, the peptide exhibited antiviral activity during co-treatment and post-treatment phases but not in pre-treatment. In vivo studies using PCV2-infected C57BL/6 mice confirmed its antiviral activity, as indicated by significantly reduced viral loads in the spleen. Mechanistically, the peptide counteracts PCV2-induced immunosuppression by restoring mRNA expression levels of type I interferons (IFN-α/β) and tumor necrosis factor-α (TNF-α) in infected cells. Furthermore, the Laby A1/A3 precursor-SUMO exhibited broad-spectrum antiviral activity of vesicular stomatitis virus (VSV), seneca valley virus (SVV), and porcine reproductive and respiratory syndrome virus (PRRSV) in a concentration-dependent manner. These findings establish Laby A1/A3 precursor-SUMO as a promising candidate for PCVAD therapy, with potential applications against multiple porcine pathogens.