Antiviral Alkaloids from : Extraction, Synergistic Effects, and Activity Against Dengue Virus and Human Coronavirus OC43

Overview

Journal Heliyon

Specialty Social Sciences

Date 2025 Mar 3

PMID 40028517

Authors

Thilina U Jayawardena

Natacha Merindol

Nuwan Sameera Liyanage

Sarah-Eve Gelinas

Berthoux Lionel

Ka Seydou

Matar Seck

Antonio Evidente

Isabel Desgagne-Penix

Affiliations

Soon will be listed here.

Abstract

, a medicinal plant from the Amaryllidaceae family, possesses potent antiviral properties attributed to alkaloids such as cherylline and lycorine. This study evaluated various extraction methods--including continuous shaking, hot solvent, microwave-assisted, ultrasound-assisted, and liquid-liquid extraction using methanol, followed by ethyl acetate and subsequent acid-base to optimize the yield of bioactive compounds. The extraction method significantly influenced phenolic acid and alkaloid precursor content, with liquid-liquid extraction yielding the highest amounts. LC-MS/MS analyses confirmed the presence of major alkaloids in the extracts, notably cherylline and lycorine. The cytotoxic and antiviral properties of extracts were assessed using a reporter-encoding dengue virus (DENV) vector and the β-coronavirus HCoV-OC43. LLE_E (liquid-liquid extract extract), enriched in phenolic compounds, was the most cytotoxic extract at concentrations above 0.6 μg/mL. Acid-base fractions, enriched in alkaloids, exhibited higher cytotoxicity than the methanol extracts counterparts, with significant cell death at concentrations above 2.5 μg/mL Additionally, the acid-base and LLE_E extracts were also the most efficient in inhibiting the replication of both HCoV-OC43 and DENV, with EC values ranging from 1 to 2.5 μg/mL. The synergistic antiviral effect of cherylline with other alkaloids was also evaluated, revealing that a combination of cherylline with gigantellinine strikingly reduced the flavivirus replication. These findings underscore the potential of as a source of bioactive compounds with antiviral properties and highlight the importance of optimizing extraction methods to enhance specific applications.

References

Baez A, Vazquez D . Binding of [3H]narciclasine to eukaryotic ribosomes. A study on a structure-activity relationship. Biochim Biophys Acta. 1978; 518(1):95-103. DOI: 10.1016/0005-2787(78)90119-3. View

Lawal I, Olufade I, Rafiu B, Aremu A . Ethnobotanical Survey of Plants Used for Treating Cough Associated with Respiratory Conditions in Ede South Local Government Area of Osun State, Nigeria. Plants (Basel). 2020; 9(5). PMC: 7286022. DOI: 10.3390/plants9050647. View

Lamoral-Theys D, Andolfi A, Van Goietsenoven G, Cimmino A, Le Calve B, Wauthoz N . Lycorine, the main phenanthridine Amaryllidaceae alkaloid, exhibits significant antitumor activity in cancer cells that display resistance to proapoptotic stimuli: an investigation of structure-activity relationship and mechanistic insight. J Med Chem. 2009; 52(20):6244-56. PMC: 3205972. DOI: 10.1021/jm901031h. View

Di Lecce R, Merindol N, Galarza Perez M, Karimzadegan V, Berthoux L, Boari A . Biochemical Analyses of Bioactive Extracts from Plants Native to Lampedusa, Sicily Minor Island. Plants (Basel). 2022; 11(24). PMC: 9788634. DOI: 10.3390/plants11243447. View

Noubissi P, Fokam Tagne M, Fankem G, Ngakou Mukam J, Wambe H, Kamgang R . Effects of Water/Ethanol Extract on -Induced Diarrhea in Rats. Evid Based Complement Alternat Med. 2019; 2019:9537603. PMC: 6434311. DOI: 10.1155/2019/9537603. View

Zou G, Puig-Basagoiti F, Zhang B, Qing M, Chen L, Pankiewicz K . A single-amino acid substitution in West Nile virus 2K peptide between NS4A and NS4B confers resistance to lycorine, a flavivirus inhibitor. Virology. 2008; 384(1):242-52. PMC: 5388927. DOI: 10.1016/j.virol.2008.11.003. View

Fennell C, Elgorashi E, Van Staden J . Alkaloid production in Crinum moorei cultures. J Nat Prod. 2003; 66(11):1524-6. DOI: 10.1021/np030206o. View

Hulcova D, Breiterova K, Siatka T, Klimova K, Davani L, Safratova M . Amaryllidaceae Alkaloids as Potential Glycogen Synthase Kinase-3β Inhibitors. Molecules. 2018; 23(4). PMC: 6017564. DOI: 10.3390/molecules23040719. View

Dai J, Mumper R . Plant phenolics: extraction, analysis and their antioxidant and anticancer properties. Molecules. 2010; 15(10):7313-52. PMC: 6259146. DOI: 10.3390/molecules15107313. View

10.

Ka S, Masi M, Merindol N, Di Lecce R, Plourde M, Seck M . Gigantelline, gigantellinine and gigancrinine, cherylline- and crinine-type alkaloids isolated from Crinum jagus with anti-acetylcholinesterase activity. Phytochemistry. 2020; 175:112390. DOI: 10.1016/j.phytochem.2020.112390. View

11.

Ka S, Merindol N, Sow A, Singh A, Landelouci K, Plourde M . Amaryllidaceae Alkaloid Cherylline Inhibits the Replication of Dengue and Zika Viruses. Antimicrob Agents Chemother. 2021; 65(9):e0039821. PMC: 8370201. DOI: 10.1128/AAC.00398-21. View

12.

Schirtzinger E, Kim Y, Davis A . Improving human coronavirus OC43 (HCoV-OC43) research comparability in studies using HCoV-OC43 as a surrogate for SARS-CoV-2. J Virol Methods. 2021; 299:114317. PMC: 8500843. DOI: 10.1016/j.jviromet.2021.114317. View

13.

Kornienko A, Evidente A . Chemistry, biology, and medicinal potential of narciclasine and its congeners. Chem Rev. 2008; 108(6):1982-2014. PMC: 2856661. DOI: 10.1021/cr078198u. View

14.

Hotchandani T, Desgagne-Penix I . Heterocyclic Amaryllidaceae Alkaloids: Biosynthesis and Pharmacological Applications. Curr Top Med Chem. 2016; 17(4):418-427. DOI: 10.2174/1568026616666160824104052. View

15.

Udegbunam S, Udegbunam R, Nnaji T, Anyanwu M, Kene R, Anika S . Antimicrobial and antioxidant effect of methanolic Crinum jagus bulb extract in wound healing. J Intercult Ethnopharmacol. 2015; 4(3):239-48. PMC: 4579492. DOI: 10.5455/jice.20150511022858. View

16.

Zhang Y, Zhang Q, Li X, Xiong J, Xiao S, Wang Z . Gemcitabine, lycorine and oxysophoridine inhibit novel coronavirus (SARS-CoV-2) in cell culture. Emerg Microbes Infect. 2020; 9(1):1170-1173. PMC: 7448857. DOI: 10.1080/22221751.2020.1772676. View

17.

Nair J, van Staden J . Cytotoxic Agents in the Minor Alkaloid Groups of the Amaryllidaceae. Planta Med. 2021; 87(12-13):916-936. DOI: 10.1055/a-1380-1888. View

18.

Girard M, Karimzadegan V, Heneault M, Cloutier F, Berube G, Berthoux L . Chemical Synthesis and Biological Activities of Amaryllidaceae Alkaloid Norbelladine Derivatives and Precursors. Molecules. 2022; 27(17). PMC: 9457815. DOI: 10.3390/molecules27175621. View

19.

Narayanan A, Narwal M, Majowicz S, Varricchio C, Toner S, Ballatore C . Identification of SARS-CoV-2 inhibitors targeting Mpro and PLpro using in-cell-protease assay. Commun Biol. 2022; 5(1):169. PMC: 8881501. DOI: 10.1038/s42003-022-03090-9. View

20.

Fischl W, Bartenschlager R . High-throughput screening using dengue virus reporter genomes. Methods Mol Biol. 2013; 1030:205-19. DOI: 10.1007/978-1-62703-484-5_17. View