Abstract
The expected progress in SARS-CoV-2 vaccinations, as anticipated in 2020 and 2021, has fallen short, exacerbating global disparities due to a lack of universally recognized "safe and effective" vaccines. This study focuses on extracts of South African medicinal plants, Artemisia annua and Artemisia afra, to identify metabolomic bioactive compounds inhibiting the binding of the SARS-CoV-2 spike protein to ACE2 receptors. The extracts were monitored for cytotoxicity using a resazurin cell viability assay and xCELLigence real-time cell analyzer. Chemical profiling was performed using UPLC-MS/MS, orthogonal projection to latent structures (OPLS), and evaluated using principle component analysis (PCA) models. Identified bioactive compounds were subjected to in vitro SARS-CoV-2 enzyme inhibition assay using standard methods and docked into the spike (S) glycoprotein of SARS-CoV-2 using Schrodinger(®) suite followed by molecular dynamics simulation studies. Cell viability assays revealed non-toxic effects of extracts on HEK293T cells at lower concentrations. Chemical profiling identified 81 bioactive compounds, with compounds like 6″-O-acetylglycitin, 25-hydroxyvitamin D3-26,23-lactone, and sesaminol glucoside showing promising binding affinity. Molecular dynamics simulations suggested less stable binding, but in vitro studies demonstrated the ability of these compounds to interfere with SARS-CoV-2 spike protein's binding to the human ACE2 receptor. Sesaminol glucoside emerged as the most effective inhibitor against this interaction. This study emphasizes the importance of multiplatform metabolite profiling and chemometrics to understand plant extract composition. This finding is of immense significance in terms of unravelling metabolomics bioactive compounds inhibiting the binding of the SARS-CoV-2 spike protein to ACE2 receptors and holds promise for phytotherapeutics against SARS-CoV-2.