Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the world at an unprecedented rate. Marine-derived sulfated polysaccharides (MSP) have received increasing attention due to their antiviral activity, especially some MSP possessed inhibitory properties against SAR-CoV-2, including fucoidan and ι-carrageenan. A more homogeneous oligo-porphyran with a mean molecular weight of 2.1 kD, named OP145, was separated from Porphyra yezoensis. The NMR analysis showed OP145 was mainly composed of →3)-β-D-Gal-(1→4)-α-L-Gal(6S) repeating units with few replacement of 3,6-anhydride of α-L-Gal, and the molar ratio of β-D-Gal, α-L-Gal(6S) and 3,6-anhydro-α-L-Gal was 1: 0.85: 0.11. MALDI-TOF MS revealed OP145 contained mainly tetrasulfate-oligogalactan with Dp range from 4 to 10 and with no more than two 3,6-anhydro-α-L-Gal replacement.
To develop novel drugs against SAR-CoV-2, the inhibitory activity of OP145 against SARS-CoV-2 was investigated in vitro. The results found OP145 showed significant antiviral activities at concentrations of 6.25–400 μg /mL with EC50 of 37.52 μg/mL. Furthermore, a test using pseudotype virus with Spike glycoprotein (S-protein) confirmed that OP145 could bind to the S-protein to prevent SARS-CoV-2 host cell entry. To evaluate the binding affinity between OP145 and S-protein, tetra-sulfated octagalactose, a dominating component of OP145 was employed to do the molecular docking experiment. Tetra-sulfated octagalactose achieved a bit stable binding of proposed binding sites with ∆G value < −5 kcal/mol (~-5.1 kcal/mol), and the dominant interactions with the key amino acid residues were of the polar type. All the results indicate that OP145 has the potential to treat and prevent COVID-19, but the structure must to be optimize to achieve higher bioactivity.