<i>Porphyra tenera</i> an Edible Red Alga Inhibits Norovirus P Domain Binding to the Host Cell Receptor

<i>Porphyra tenera</i> (PT), an edible red alga, is consumed as a health-promoting seaweed. Human norovirus (HuNV), the major cause of foodborne disease outbreaks worldwide, binds to histo-blood group antigens (HBGAs) for cell entry. We investigated the inhibitory activity of fucose-containing polysaccharides in PT on HuNV binding to the HBGAs. With saliva as a source of HBGAs and recombinant P domains of HuNV GII.4 and GII.17 purified as NV antigens, the inhibition and binding affinity of PT toward P domains were evaluated using enzyme-linked immunosorbent assay and bio-layer interferometry, respectively. The PT polysaccharide extract and its 3-10 kDa fraction (F3-10) among molecular weight fractions inhibited the P domain binding to saliva significantly, compared with that of a commercial fucoidan. F3-10 bound directly to the P domains with submicromolar affinities (K_D = 5.6 × 10^-7 M for GII.4 and 8.7 × 10^-7 M for GII.17). When applied to virus inhibition assays, F3-10 significantly reduced murine NV titers in a dose-dependent manner; specifically, it showed a 1.8 log₁₀ plaque forming unit (PFU)/mL reduction at 1 mg/mL in RAW 264.7 cells (<i>p</i> < 0.05) and a 1.4 log₁₀ PFU/mL reduction at 5 mg/mL under simulated human digestion conditions involving sequential incubation in simulated saliva, gastric, and intestinal fluids (<i>p</i> < 0.01). F3-10 contained galactose, glucose, fucose, and xylose as its constituent monosaccharides and also sulfate groups. The PT fraction F3-10 is a promising candidate for further study aimed at inhibiting HuNV binding to host cell HBGAs.