Deciphering the Effects of <i>Pterocarpus mildbraedii</i> and <i>Pterocarpus soyauxii</i> Against Sars-CoV-2 and HIV Coinfection through the Integration of ADMET, Network Pharmacology, <i>in silico</i> Molecular Docking, Pharmacophore Analysis and Co

This research explored the therapeutic efficacy of bioactive substances derived from Pterocarpus soyauxii and Pterocarpus mildbraedii against HIV-1 and SARS-CoV-2 co-infection. Pharmacokinetic characteristics were evaluated with ADMETlab 3.0. Network pharmacology analyses were conducted using Swiss Target Prediction, GeneCards, STRING, Cytoscape and Metascape, along with pathway mapping in Srplot. The protein structures of EGFR, MMP9 and SARS-CoV-2 polyprotein 1ab were assessed through the SwissModel and ProSA-web databases. Molecular docking and binding sites determination were performed through 1-Click Docking and BC-Dock2 web servers. Inhibitory activity of the compounds on the CDK2 and HIV-1 proteins was carried out in the kinCSM way2drug databases. Results show that Khrinone A and E exhibited positive absorption and distribution profiles. Network pharmacology revealed essential molecular targets and enriched KEGG pathways associated with viral replication. MolProbity scores ranged from 0.77 to 2.28, with over 92% of residues located in Ramachandran preferred regions. Molecular docking revealed significant binding affinities, especially Pterocarpin (−9.9 kcal/mol) with MMP9 and Khrinone A (−8.9 kcal/mol) with NOS2, surpassing reference inhibitors. In comparison to EGFR, the affinities of natural ligands (−7.7 kcal/mol to −7.0 kcal/mol) were similar to Gefitinib, whereas Claussequinone and Khrinone E demonstrated compelling interactions with HIV-1 reverse transcriptase (−7.4 kcal/mol to −7.2 kcal/mol), resembling those of Lawsone (−8.3 kcal/mol). Additionally, Khrinone A and E can serve as potent CDK2 inhibitors ([Formula: see text]), exhibiting pKi values (5.902–5.929) comparable to those of Palbociclib (6.029). These results indicate that compounds derived from Pterocarpus have multitarget antiviral and host-modulating abilities, reinforcing their potential as valuable candidates for therapeutic intervention in HIV/SARS-CoV-2 co-infection.