Evaluation of the potential of botanicals and their constituents against the SARS-CoV-2 virus

Abstract

The critical challenge that natural products research projects seek to address is identifying biologically active constituents in complex mixtures. The gold standard approach towards this goal is bioassay-guided fractionation, whereby mixtures are successively purified and tested for their ability to achieve a desired biological activity. The success of this approach is reflected by the discovery of many essential drugs, including the antibiotics streptomycin and tetracycline, and the anti-cancer drug Taxol. However, the bioassay-guided fractionation approach is limited by i) its inherent bias towards abundant and easily isolable compounds, and ii) the quality of the biological data used to guide isolation. The Center for High-Throughput Functional Annotation of Natural Products (HiFAN) seeks to address these limitations by developing new tools for the comprehensive evaluation of natural product mixtures. These tools enable the collection of multi-dimensional biological datasets, and the application of untargeted spectrometry metabolomics approaches to comprehensively profile the chemical composition of natural product mixtures. We will highlight the application of these approaches to identify natural product extracts and constituents with potential efficacy against SARS-CoV-2. A panel of botanical extracts and pure natural compounds were screened for blockade of authentic SARS-CoV-2 infection in cell culture. Promising activity was demonstrated by extracts and constituents from the botanical Stephania tetrandra, and the chemical and biological datasets were integrated using a multivariate statistical approach to determine which active constituents were most strongly associated with biological activity. We are currently employing HiFAN’s gene expression and cytological profiling platforms to derive insight into potential anti-viral and anti-inflammatory mechanisms of action for the bioactive constituents.