SARS-CoV-2 inhibitory potential of fish oil-derived 2-pyrone compounds by acquiring linoleic acid binding site on the spike protein.

ABSTRACT

Traditional medicines have reportedly treated SARS-CoV-2 infection. Substantial evidence shows that fish oil supplements promote human immune function, suggesting they may lessen susceptibility to SARS-CoV-2 infection and suppress viral replication by inducing interferon. Fish oil was subjected to partition chromatography and separated into two compounds (EP01 and DH01). Isolated compounds were purified and characterized using UV, FTIR, NMR, and mass spectrometry to confirm their identity. Molecular docking was studied on the SARS CoV-2 variants of concern; SARS CoV-2 WT (PDB 6VXX), SARS CoV-2 Alpha variant (PDB 7LWS), SARS CoV-2 Delta variant (PDB 7TOU), SARS CoV-2 Gamma variant (PDB 7V78), SARS CoV-2 Kappa variant (PDB 7VX9), and SARS CoV-2 Omicron variant (PDB 7QO7) and TMPRSS2 (PDB 7Y0E). Further selected protein-ligand complexes were subjected to 100 ns MD simulations to predict their biological potential in the SARS-CoV-2 treatment. In-vitro biological studies were carried out to support in-silico findings. Isolated compounds EP01 and DH01 were identified as 5-Tridecyltetrahydro-2H-pyran-2-one and 5-Heptadecyltetrahydro-2H-pyran-2-one, respectively. The compound EP01 significantly reduced (93.24 %) the viral RNA copy number with an IC50 of ~8.661 µM. EP01 proved to be a potent antiviral by in-vitro method against the SARS-CoV-2 clinical isolate, making it a promising antiviral candidate, with a single dose capable of preventing viral replication.