Aloperine-type alkaloids from Sophora alopecuroides as promising reverse transcriptase inhibitors for human and feline immunodeficiency viruses: Structure-based evaluation

The study aimed to estimate the potential of 21 Aloperine-based alkaloids obtained from the extract of Sophora alopecuroides against the reverse transcriptase enzymes of the feline immunodeficiency virus (FIV-RT) and the human immunodeficiency virus (HIV-RT). These enzymes are essential for viral replication. This study uses a structure-based virtual screening approach, including molecular docking simulations and pharmacokinetic prediction. The 21 alkaloids based on alloperine had their chemical structure optimized using the Merck Molecular Force Field (MMFF94) method and prepared for the molecular docking simulations , which were performed using the AutoDockVinaTM, targeting FIV-RT (PDB: 5OVN ) and HIV-RT (PDB: 3HVT ), taken from the RCSB Protein Data Bank repository. Pharmacokinetic descriptors were analyzed from the properties of intrinsic lipophilicity (logP) and at physiological pH (logD7.4), while organic toxicity was predicted by metabolism site analysis. The molecular docking study showed that Aloperines 1, 3, 9, 19, and 21 presented the most significant affinity energy values by binding to the FIV-RT. Against HIV-RT, it can be concluded that Aloperine 13 may be promising as it interacts with the binding site of rilpivirine and the co-crystallized inhibitor nevirapine , in addition to interactions with the conserved residues Leu-234 and Tyr-319. However, Aloperine 9 is estimated to have more favorable drug-like properties, indicating a more significant pharmacokinetic potential among the evaluated derivatives. This study offers initial insights into the promising activity of alloperine-based alkaloids in the treatment of FIV and HIV, constituting the starting point for future experimental validation.