A blueberry-derived polysaccharide inhibits SARS-CoV-2 papain-like protease and exhibits broad-spectrum anti-coronavirus activity.

Vaccinium corymbosum (blueberry) is widely regarded as a functional food, the antiviral potential of blueberry polysaccharides has not yet been explored. In this study, a polysaccharide fraction designated 2B4 was isolated from blueberry fruits, and its potential inhibitory activity against the SARS-CoV-2 papain-like protease (PLpro)-a key enzyme involved in viral replication and immune evasion-was examined in detail. Chemical analysis and spectrum analysis results showed that 2B4 is a heterogeneous polysaccharide with an average molecular weight of 54.074 kDa, can be characterised as an acidic, branched heteropolysaccharide, containing both neutral and uronic sugar residues. In vitro assays demonstrated that 2B4 strongly inhibited SARS-CoV-2 PLpro activity. Kinetic binding analysis further indicated that 2B4 directly interacts with PLpro. At the cellular level, 2B4 displayed excellent safety and dose-dependent inhibition of HCoV-OC43 replication. This work offers a new perspective and experimental foundation for the development of natural antiviral candidates from edible and medicinal plants.