Seaweeds: Nature's super therapeutics? Immunomodulatory and anti-viral properties of sulfated rhamnoxyloglucuronan isolated from Ulva fasciata Delile

Green seaweeds, which make up a major population of total seaweed worldwide, possess various therapeutic properties. The aim of the study directed at isolating a (1 → 4) linked sulfated rhamno xyloglucuronan, designated as UFP-2, from the edible green seaweed Ulva fasciata Delile, and to evaluate its efficacy in modulating immune responses and inhibiting SARS-CoV-2 (Delta variant) infection. Anti-inflammatory potential of UFP-2 was demonstrated through the regulation of key cytokines involved in inflammatory responses triggered by viral infections, including interferons (IFN-α/γ), interleukin (IL-1β/12/33), and tumor necrosis factor (TNF-α). Confocal microscopy and flow cytometry analyses indicated downregulation of IFN-α and IL-1β, while TNF-α expression reduced from 29.28 % in lipopolysaccharide (LPS)-induced CALU-1 cells to 1.6-5.4 % upon UFP-2 treatment. Treatment with UFP-2 at a concentration of 125 μg/mL significantly downregulated the overexpression of IL-1β in SARS-CoV-2-infected CALU-1 cells. Administering UFP-2 to SARS-CoV-2 (delta variant) induced cells led to increased cell viability and higher cycle threshold (Ct) values (20.34), indicating reduced viral load, with viral copy numbers decreasing from over 6.5 × 10⁷ to <2.5 × 10⁷ per cell. Structure-activity relationship analysis suggested that sulfate groups and overall hydrophilicity of UFP-2 contribute to its binding affinity with target receptors, potentially disrupting viral entry and replication processes.