Identification of botanical viral entry inhibitors for SARS-CoV-2

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FASEB J. 2022 May;36 Suppl 1. doi: 10.1096/fasebj.2022.36.S1.R5609.


Examining biodiversity across the globe has always been a vital part of drug development and has led to the discovery of common drugs for many medical issues, including pain management, cancer, heart disease, and heart disease. infections. During the SARS-CoV-2 pandemic, the use of natural supplements in the United States increased. The effectiveness of these natural products in preventing SARS-CoV-2 infection and the safety of their use remain unexplored; therefore, more research should be done to determine which supplements have antiviral properties. The Quave Natural Product Library (QNPL) is a collection of over 2,000 botanical and fungal extracts and includes the 40 most widely used natural supplements in the United States. Collecting biological samples for the library requires field expeditions to areas of the world with high levels of biodiversity. Each of these extracts was tested in a SARS-CoV-2 pseudotyped virus system to determine which extracts inhibit viral entry, specifically the virus spike protein binding to host cell ACE2 receptors. Cytotoxicity tests on mammalian cells were carried out in parallel. Evaluation of 1,887 extracts and 18 unique compounds of QNPL against SARS-CoV-2 identified. 317 extracts derived from 134 species from 76 families (1 lichen, 2 fungi, 73 plant families) showed ≥50% inhibitory activity in the pseudotyped wild-type ear model at 20 µg/mL. Among these bioactive extracts, 129 extracts derived from 95 plant species showed inhibition activity ≥ 85% and cytotoxicity ≤ 15% in the wild-type model. Once these 129 extracts were identified, an interesting pattern emerged indicating that many results came from species known to be cardiotoxic due to their rich composition of cardiac glycosides. For further screening and testing, we reviewed each extract and searched the literature to weed out extracts with these properties or similar compounds, narrowing our interest to 8 extracts. These extracts were then validated in a concentration-response test in a pseudotyped virus model. The EC50 the values ​​of the 3 best extracts were all below 10 µg/mL. These 3 extracts all showed activity (≥85% inhibitory activity) in wild-type and variant pseudotyped models. Tests on live SARS-CoV-2 confirmed the antiviral activity of 2 of the 3 extracts, the flowers of plant A and the roots of plant B. Further chemical characterization of the main metabolites of these two hits was performed using MS/MS fragmentation data compared to literature, in silico prediction and web databases. The results revealed that phenylpropanoids, flavonoids, triterpenes, glycosidic terpenes and fatty acids were the main chemical classes. The next steps of this study aim to identify and isolate the purified bioactive compounds to better understand their role in the inhibition of SARS-CoV-2.

PMID:35555940 | DOI:10.1096/fasebj.2022.36.S1.R5609

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