Use of hyphenated analytical techniques to isolate and characterise antiviral compounds against SARS-CoV-2 from South African medicinal plants

Abstract

The SARS-CoV-2 virus and, as an extension, the COVID-19 pandemic has led to unprecedented damage, economic hardship, and mental and/or physical strain on a global scale and highlighted humanity’s need for adequate pandemic preparedness. Amongst this, drug development remains one of the fundamental cornerstones to conquering the challenges associated with a novel virus or disease. Traditionally used medicinal plants and natural products play an essential role in treating and managing many diseases of both an infectious and non-infectious origin. South Africa has an extensive biodiversity, amongst the top in the world, with ca. 3000 South African plants used in traditional medicine, ca. 250 of which are used for treating respiratory illnesses. Through the use of an in-depth database search and screening criteria, a subset of South African plants were selected for biological screening against the SARS-CoV-2 virus in an high throughput screening manner. Of the 147 plant fractions screened, 37 were found to have good antiviral activity against the SARS-CoV-2 main protease or spike protein. Of the plants screened, three widely-used traditional plants exhibited potent antiviral activity against the SARS-CoV-2 virus, viz., Gunnera perpensa, Siphonochilous atheopicus and Podocarpus henkelii and were prioritised for comprehensive chemical and biological investigation in a bid to identify their bioactive counterparts. Six bioactive compounds viz., the hydroxylated lactone of siphonochilone (25), punicalin (23), α/β-punicalagin (18), lespedezic acid (17), inumakilactone B (52) and sandaracopimaric acid (53) were successfully isolated and identified through the use of hyphenated analytical techniques which included UPLC-IMS-HRMS, SCXRD and NMR spectrometry. By employing in silico molecular docking, the bioactive compound’s respective mechanisms of action were predicted. Through this work, it can be concluded that South African medicinal plants present exciting opportunities for developing new antiviral agents against the SARS-CoV-2 virus to complement ongoing vaccination efforts.