The pan-African natural products library compounds oleanolic acid, poinsettifolin B, and rhuschalcone III disrupt SARS-CoV-2 spike-host ACE2 interactions and SARS-CoV-2 replication.
14 affiliations
- 1Center for Drug Discovery, Faculty of Science, University of Buea, P. O. Box 63, Buea, Cameroon.
- 2Department of Chemical Biology, Faculty of Science, University of Bertoua, P. O. Box 416, Beroua, Cameroon.
- 3University Institute of Wood Technology, University of Yaoundé 1, Mbalmayo Campus, Mbalmayo, Cameroon.
- 4Department of Physics, Ecole Normale Supérieure, University of Yaoundé 1, P. O. Box 47, Yaoundé, Cameroon.
- 5Department of Chemistry, Faculty of Science, University of Buea, P. O. Box 63, Buea, Cameroon.
- 6Structural Genomics Consortium, University of Toronto, Toronto, ON, M5G 1L7, Canada.
- 7Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, M5S 1A8, Canada.
- 8The Wistar Institute, Philadelphia, PA, 19104, USA.
- 9Department of Biological Sciences, University of Botswana, Gaborone, Botswana.
- 10Center for Drug Discovery, Faculty of Science, University of Buea, P. O. Box 63, Buea, Cameroon. [email protected].
- 11Department of Chemistry, Faculty of Science, University of Buea, P. O. Box 63, Buea, Cameroon. [email protected].
- 12Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany. [email protected].
- 13The Wistar Institute, Philadelphia, PA, 19104, USA. [email protected].
- 14School of Business, Arts, and Sciences, Delaware Valley University, Doylestown, PA, 18901, USA. [email protected].
Abstract
Natural product (NP)-based chemical libraries are a rich source of antiviral compounds that can serve as the basis for new therapeutic leads to treat viral diseases, particularly for individuals lacking sustained access to existing vaccines and therapeutics. To identify new NP-based candidate inhibitors of SARS-CoV-2 cellular entry and viral replication, we screened the pan-African Natural Products Library (p-ANAPL), a collection of physical pure compounds obtained from African medicinal plants, for NPs that can disrupt the in vitro interaction of the SARS-CoV-2 Spike receptor-binding domain (RBD) with its host ACE2 entry receptor. This screen identified three compounds - oleanolic acid, poinsettifolin B, and rhuschalcone III - which disrupt RBD/ACE2 interactions with half-maximal inhibitory concentrations (IC₅₀s) of 0.5-2.4 µM but do not disrupt an unrelated PD-1/PD-L1 host ligand/receptor binding pair. Oleanolic acid and rhuschalcone III, but not poinsettifolin B, additionally inhibited SARS-CoV-2 replication in Vero cells without cytotoxicity at low micromolar concentrations. Computational modelling indicated that all three compounds interact with numerous RBD and ACE2 residues, including a subset conserved across SARS-CoV-2 variants of concern. Taken together, we identify three NPs that selectively interfere with factors involved in SARS-CoV-2 entry and/or viral replication, representing new antiviral leads for COVID-19 management in resource-limited areas.
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BibTeX
@article{tjegbe2026panafrican,
title = {{The pan-African natural products library compounds oleanolic acid, poinsettifolin B, and rhuschalcone III disrupt SARS-CoV-2 spike-host ACE2 interactions and SARS-CoV-2 replication.}},
author = {Mathieu J M Tjegbe and Pascal Amoa Onguéné and Boris D Bekono and Jude Y Betow and Conrad V Simoben and Joel Cassel and Joseph M Salvino and Luis J Montaner and Kerstin Andrae-Marobela and Fidele Ntie-Kang and Ian Tietjen},
journal = {BMC pharmacology \& toxicology},
year = {2026},
month = oct,
doi = {10.1186/s40360-026-01264-3},
url = {https://europepmc.org/article/MED/42919422},
note = {CC BY},
}
RIS
TY - JOUR
TI - The pan-African natural products library compounds oleanolic acid, poinsettifolin B, and rhuschalcone III disrupt SARS-CoV-2 spike-host ACE2 interactions and SARS-CoV-2 replication.
AU - Mathieu J M Tjegbe
AU - Pascal Amoa Onguéné
AU - Boris D Bekono
AU - Jude Y Betow
AU - Conrad V Simoben
AU - Joel Cassel
AU - Joseph M Salvino
AU - Luis J Montaner
AU - Kerstin Andrae-Marobela
AU - Fidele Ntie-Kang
AU - Ian Tietjen
PY - 2026
DA - 2026/10/21
JO - BMC pharmacology & toxicology
DO - 10.1186/s40360-026-01264-3
UR - https://europepmc.org/article/MED/42919422
AB - Natural product (NP)-based chemical libraries are a rich source of antiviral compounds that can serve as the basis for new therapeutic leads to treat viral diseases, particularly for individuals lacking sustained access to existing vaccines and therapeutics. To identify new NP-based candidate inhibitors of SARS-CoV-2 cellular entry and viral replication, we screened the pan-African Natural Products Library (p-ANAPL), a collection of physical pure compounds obtained from African medicinal plants, for NPs that can disrupt the in vitro interaction of the SARS-CoV-2 Spike receptor-binding domain (RBD) with its host ACE2 entry receptor. This screen identified three compounds - oleanolic acid, poinsettifolin B, and rhuschalcone III - which disrupt RBD/ACE2 interactions with half-maximal inhibitory concentrations (IC₅₀s) of 0.5-2.4 µM but do not disrupt an unrelated PD-1/PD-L1 host ligand/receptor binding pair. Oleanolic acid and rhuschalcone III, but not poinsettifolin B, additionally inhibited SARS-CoV-2 replication in Vero cells without cytotoxicity at low micromolar concentrations. Computational modelling indicated that all three compounds interact with numerous RBD and ACE2 residues, including a subset conserved across SARS-CoV-2 variants of concern. Taken together, we identify three NPs that selectively interfere with factors involved in SARS-CoV-2 entry and/or viral replication, representing new antiviral leads for COVID-19 management in resource-limited areas.
SN - 2050-6511
ER -