Pulmonary Phospholipid Components as Promising Natural Inhibitors against COVID-19 Mpro; Molecular Docking Analysis Based Study

Abstract

The ongoing pandemic of COVID-19 caused by the severe acute respiratory syndrome SARS-CoV-2 has become a global crisis. Phospholipids are structural components of mammalian cell membranes that suppress viral attachment to the plasma membrane and subsequent replication in lung cells. Using the molecular docking approach, the inhibitory activity of phosphatidylcholine, dipalmitoylphosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, lysobisphosphatidic acid and sphingomyelin against SARS CoV-2 by targeting main protease (Mpro, PDB code: 6LU7) has been investigated. All phospholipids established excellent binding to Mpro active bocket by forming several H-bonds with the catalytic amino acids Cys145 and His4, as well as various amino acids involved in the bocket. Furthermore, a potent binding affinity is increased from -7.01 to -9.16 kcal/mol compared to compound N3 (N-[(5-methylisoxazol-3-yl)carbonyl]alanyl- L (where L = valyl-N-1-(1R,2Z)-4-(benzyloxy)-4-oxo-1-{[(3R)-2-oxopyrrolidin-3-yl]methyl}but-2- enyl)-L-leucinamide), a peptide linker, inhibitor for Covid-19 main protease. Co-crystalline ligand of enzyme 6LU7 of -9.99 kcal/mol. The sphingomyelin has the same binding affinity to main protease when compared to compound N3. These findings implied that the selected compounds have the potential to be developed as novel SARS-CoV-2 inhibitors. Therefore, improved, well-designed, potent and structurally and pharmacokinetically effective drugs are urgently needed. Further investigations should focus on validating and finalizing effective drugs for COVID-19 beyond preliminary in silico and in vivo screening.