Fucoidans are a class of long chain sulfated
polysaccharides and have multiple biological functions. Herein, four natural fucoidans extracted from Fucus vesiculosus, F. serratus, Laminaria japonica and Undaria pinnatifida, were tested for their HCoV-OC43 inhibition and found to demonstrate EC50 values ranging from 0.15 to 0.61 µg/mL. That from U. pinnatifida exhibited the most potent anti-HCoV-OC43 activity with an EC50 value of 0.15 ± 0.02 µg/mL, a potency largely independent of its
sulfate content. Comparison of the gene expression profiles of
fucoidan-treated and untreated cells infected with HCoV-OC43 revealed that
fucoidan treatment effectively diminished HCoV-OC43 gene expressions associated with induced
chemokines,
cytokines and viral activities. Further studies using a highly
fucoidan-resistant HCoV-OC43 determined that
fucoidan inhibited HCoV-OC43
infection via interfering with viral entry and led to the identification of the specific site on the N-terminal region of spike
protein, that located adjacent to the host cell receptor binding domain, targeted by the virus. Furthermore, in a SARS-CoV-2 pseudovirus neutralization assay,
fucoidan also blocked SARS-CoV-2 entry. In vitro and in vivo,
fucoidan decreased SARS-CoV-2 viral loads and inhibited
viral infection in Calu-3 or Vero E6 cells and SARS-CoV-2 infected hamsters, respectively.
Fucoidan was also found to inhibit
furin activity, and reported
furin inhibitors were found to inhibit
viral infection by wild type HCoV-OC43 or SARS-CoV-2. Accordingly, we conclude that fucoidans inhibit coronaviral
infection by targeting viral spike
protein and host cell
furin to interfere with viral entry.