Activities of fungal metabolites sphaeropsidin A and B to fight against canine coronavirus

Pimarane diterpenes represent a notable class of metabolites. Secondary metabolites sphaeropsidin A (SphA) and sphaeropsidin B (SphB), produced by phytopathogenic fungi, have been recently reported for their potential efficacy against bovine coronavirus (BCoV). Hence, for discovering natural antivirals to serve as alternatives to conventional drugs, in this study the efficacy of SphA and SphB during infection with canine coronavirus (CCoV-II) in A72 cell line was examined. Our results demonstrated that a significant reduction in virus yield and in gene and protein expression of viral nucleocapsid protein (NP) was detected in sphaeropsidins (Sphs)-treated infected cells. In infected groups both Sphs enhanced cell viability and improved cellular morphology as well as cytoskeleton rearrangements. Moreover, the protein expression of aryl hydrocarbon receptor (AhR), a strategic modulator of CoVs infection, and of its target CYP1A1, was markedly downregulated in the presence of SphA and SphB during infection. These results were accompanied by a beneficial deacidification of lysosomal environment in infected cells treated with SphA and SphB compared to untreated-infected groups. Overall, our findings demonstrated a promising action of SphA and SphB towards CCoV infection in vitro.