Molecular docking and molecular dynamics study of PUFAs from Navicula salinicola: prospective antiviral strategies targeting the SARS-CoV-2 spike protein.

The emergence of novel viral infections, such as SARS-CoV-2, H5N2, and H7N9, among recently identified viruses, has highlighted the urgent need for new antiviral therapeutics. The SARS-CoV-2 virus binds to ACE2 on host cell surfaces, reducing ACE2 expression, increasing Angiotensin II, and activating the RAAS system. On the other sides, marine organisms like Navicula salinicola are a significant unexplored source of bioactive compounds with potential antiviral activity. However, investigation on marine-derived poly-unsaturated fatty acids (PUFAs) as antiviral agents for SARS-CoV-2 is a priority, as they have shown promising antiviral properties. This exploration highlights the ongoing efforts to explore natural compounds for their therapeutic potential against viral infections, including COVID-19. This study aims to investigate the antiviral potential of PUFAs from N. salinicola against SARS-CoV-2 using molecular docking and molecular dynamics simulations. A total of 14 PUFAs from N. salinicola were subjected to molecular docking with the SARS-CoV-2 spike protein, and the three best-ranked ligands, DHA (- 7.56 kcal/mol), AA (- 6.61 kcal/mol), and EPA (- 6.5 kcal/mol), were further analyzed by molecular dynamics. Our study identified all PUFAs with promising binding affinities toward the SARS-CoV-2 spike protein, suggesting their potential as effective inhibitors of viral entry or replication mechanisms. Molecular dynamics simulations revealed that the ligands docosahexaenoic acid (DHA), arachidonic acid (AA), and eicosapentaenoic acid (EPA) exhibited ∆ETotal values of - 46.45, - 48.31, and - 43.65 kcal/mol, respectively, indicating a relatively stable interaction with ACE2. AA, the most potent marine-derived PUFA from N. salinicola, has been identified as the lead compound for SARS-CoV-2 inhibitors, requiring further research for in vitro or in vivo experiments.