Abstract
Dodonaea viscosa is one of the widely distributed ornamental plants. It is rich in many phytoconstituents. The present study aims to examine the activity of spanlastics formulations loaded with compounds isolated from Dodonaea viscosa leaves extract. The isolated compounds were identified and loaded into nanovesicles. The anti-SARS-CoV-2 activity of selected drug-loaded spanlastics was evaluated using MTT assay and the underlying mechanism of action was determined. The formulations showed high encapsulation efficiency with vesicle diameters in the nanometre range. The vesicles were spherical and exhibited large negative values of zeta potential, indicating good stability. Selected formulations of V and S (V1 and S1) exhibited high antiviral activity against SARS-CoV-2 with IC50 of 4.483 and 9.795 µg/ml for V1 and S1, respectively, through inhibition of virus adsorption for V1 and virucidal activity by 55.7 % for S1. The network pharmacology defined the EGFR as the top annotated gene with 7 edges, followed by PIK3CG, VEGFA, and MMP9 genes with 4 edges for each. Molecular docking simulations reveal favourable binding affinities and diverse interactions with critical amino acid residues. In silico ADMET profiling further indicated that both compounds are drug-like, with favourable absorption and core-safety signatures (non-mutagenic, non-carcinogenic, and non-cardiotoxic). Santin and viscosine formulated nanovesicles represent promising formulations with therapeutic potential against SARS-CoV-2.