Discovery of potential inhibitors from Linum grandiflorum Desf. against HIV-1 RT, in vitro, molecular docking and molecular dynamics simulation supported study

The human immunodeficiency virus inhibitory action of the hexane and pet. ether extracts of Linum grandiflorum seeds and leaves was evaluated using MTT assay, against the multiplication of HIV-1_IIIB wild type, N119, A17 and EFVR in acutely infected cells. With promising outcomes expressed with ED₅₀ = 43µM, the thing that, pushed our effort to unveil the chemical composition of the propitious extract, using GC/MS to analysis the fatty acid constituents revealed the identification of myristic, palmitic, stearic, oleic, linoleic and linolenic acids. The dynamic behaviour, binding interactions and protein–ligand stabilities have also been investigated using the molecular docking and molecular dynamics (MD) simulation research. The molecular docking proved stability fitting of all FAs inside the catalytic domain of HIV-1 RT, with negative binding affinities with molecular H-bonding and hydrophobic interactions. Additionally, the MD simulation proved complex stability, compactness, low fluctuations of the amino acid residues at the key binding pocket as a consequence of RMSD, RMSF, RoG, SASA and cluster analyses. Surprisingly, MM/PBSA calculations resulted with highly negative binding free energies for all the tested hits.