Abstract
Ethnopharmacological relevance: Plants and fungi have a long tradition in ethnopharmacology for the treatment of infectious diseases including viruses. Many of these natural products have also been used to combat SARS-CoV-2 infections or symptoms of the post- and long-COVID form, owing to the scarcity of clinically approved therapeutics. Aim of the study: The ongoing threat posed by SARS-CoV-2, along with the rapidly evolving new variants, requires the development of new antiviral compounds. The aim of this study was to identify anti-SARS-CoV-2 herbal and fungal extracts used in traditional medicine against acute respiratory infection, inflammation, and related symptoms. Additionally, we sought to characterize their bioactive constituents. Materials and methods: The antiviral activity and cell cytotoxicity of 179 herbal and fungal extracts were evaluated using two SARS-CoV-2 infection assays in Caco-2 cells. 19 plant extracts with and without anti-SARS-CoV-2 activity underwent detailed dereplication using molecular networking. Results: Extracts from Angelica sinensis (Oliv.) Diels roots, Annona squamosa L. seeds, Azadirachta indica A. Juss. fruits, Buddleja officinalis Maxim. flowers, Burkea africana Hook. bark and Clinopodium menthifolium (Host) Stace aerial parts showed a potent anti SARS-CoV-2 activity (IC50 < 5 μg/ml) with only moderate cytotoxicity (CC50 > 60 μg/ml, Caco-2). By performing the dereplication with a bioactivity-featured molecular network (MN) on the extract library level, rather than on the level of individual extracts, we could pinpoint compounds characteristic for active extracts. Thus, a straight-forward identification of potential anti-SARS-CoV-2 natural compounds was achieved prior to any fractionation or isolation efforts. Conclusions: A sophisticated hyphenation of empirical knowledge with MS-based bioinformatics and automated compound annotation was applied to decipher the chemical space of the investigated extracts. The correlation with experimentally assessed anti-SARS-CoV-2 activities helped in predicting compound classes and structural elements relevant for the antiviral activities. Consequently, this accelerated the identification of constituents from the investigated mixtures with inhibitory effects against SARS-CoV-2.
| Original language | English |
|---|---|
| Article number | 117206 |
| Journal | Journal of Ethnopharmacology |
| Volume | 319 |
| Issue number | Part 2 |
| Early online date | 30 Sept 2023 |
| DOIs | |
| Publication status | Published - 30 Jan 2024 |
Funding
This work was funded by the Austrian Science Fund (FWF, P34028 and P35115 ). The authors thank R. Blažević, (Department of Pharmaceutical Sciences, Division of Pharmacognosy, University of Vienna, Austria) for technical assistance, L. Michaelis (Department of Pharmaceutical Sciences, Division of Pharmacognosy, University of Vienna, Austria) for proofreading, and J. Orts and M. J. Abi Saad (Division of Pharmaceutical Chemistry, Department of Pharmaceutical Sciences, University of Vienna, Austria) for the production and purification of SARS-CoV-2 M pro . The extract library was first screened for anti-SARS-CoV-2 activity with a pre-screening assay in Caco-2-F03 cells at two concentrations (50 μg/mL and 0.5 μg/mL). The assay is based on an indirect readout of the anti-SARS-CoV-2 activity, which is determined by measurement of the inhibition of viral-induced caspase 3/7 activity 48 h post-infection. In total, 34 extracts showed a caspase inhibition of more than 60% at 50 μg/mL and were thus classified as active resulting in a hit rate of 18.9% (Table S1). Furthermore, extracts E9, seeds of Annona squamosa L., and E100, flowers of Matricaria chamomilla L., even showed significant inhibitory activities at 0.5 μg/mL with 108.74% and 41.88%, respectively. Furthermore, the obtained results support the previously reported anti-SARS-CoV-2 activity of extracts from Andrographis paniculata (Burm.f.) Wall herb (E6), Magnolia sp., flowers (E99), Scutellaria baicalensis Georgi roots (E144) and Withania somnifera (L.) Dunal leaves and herb (E174, E175) (Chakraborty et al., 2022; Liu et al., 2021; Sa-ngiamsuntorn et al., 2021; Wasilewicz et al., 2023a) and were therefore not in the focus of further investigations. In addition, the extracts of Cynara cardunculus L. leaves (E40), Fomitopsis pinicola (Sw.) P. Karst. fruit body (E56), Ipomoea nil (L.) Roth seeds (E82), Salvia rosmarinus Schlied. leaves (E138), Vincetoxicum mukdenense Kitag. roots (E169) and Vincetoxicum stauntonii (Decne.) C.Y.Wu & D.Z.Li roots (E170) were excluded from further research due to cell cytotoxicity as previously reported (Grienke et al., 2018a).This work was funded by the Austrian Science Fund (FWF, P34028 and P35115). The authors thank R. Blažević, (Department of Pharmaceutical Sciences, Division of Pharmacognosy, University of Vienna, Austria) for technical assistance, L. Michaelis (Department of Pharmaceutical Sciences, Division of Pharmacognosy, University of Vienna, Austria) for proofreading, and J. Orts and M. J. Abi Saad (Division of Pharmaceutical Chemistry, Department of Pharmaceutical Sciences, University of Vienna, Austria) for the production and purification of SARS-CoV-2 Mpro.
Austrian Fields of Science 2012
- 301204 Pharmacognosy
