Promising alkaloids and flavonoids compounds as anti-hepatitis C virus agents: a review


Published: 16 March 2023
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Authors

  • Gusti Rizaldi Master Program in Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia.
  • Achmad Fuad Hafid Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya; Center for Natural Products Medicine Research and Development, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.
  • Tutik Sri Wahyuni Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya; Center for Natural Products Medicine Research and Development, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.

Background: Virus infections are presently seen as a major public health problem. Hepatitis C Virus (HCV) is recognized as a “silent killer” because the acute infection has no symptoms, and it develops as a chronic infection that causes hepatocellular carcinoma and liver damage. The World Health Organization (WHO) predicts that between 130-170 million people are estimated to have chronic Hepatitis C. Plants have various phytochemical compounds such as alkaloids and flavonoids that have prominent antiviral effects especially anti-HCV. The current HCV treatment still has limitations related to side effects and can lead to viral resistance. Therefore, it is necessary for the discovery and development of novel anti-HCV drugs for alternative and complementary medicine.

Objective: This review intends to evaluate the alkaloids and flavonoids that have the potential to be used against HCV by looking at their classification and their mechanism of action.

Methods: Twenty-one articles from 2010 to 2022 obtained from PUBMED database using keywords such as isolated compounds, alkaloids, flavonoids, hepatitis C virus.

Results: 21 alkaloids and 37 flavonoids reported active against HCV. Alkaloids include quinoline, quinolizidine and isoquinoline. In addition, flavanone, flavonol, flavone, flavan-3-ol, flavonolignan, anthocyanidin and proanthocyanidin comprise flavonoids. The berberine alkaloids and eriodictyol 7-O-(6′′-caffeoyl)-β-D- glucopyranoside flavonoids had the lowest IC50 with values of 0.49 mM and 0.041 nM.

Conclusions: Alkaloids and flavonoids compound had good activity against HCV with various mechanisms. Our results provide information of alkaloids and flavonoids to the researcher for the development of alternative and complementary medicine of hepatitis C.


Antonio ADS, Wiedemann LSM, Veiga-Junior VF. Natural products’ role against COVID-19. RSC Adv 2020;10:23379–93. DOI: https://doi.org/10.1039/D0RA03774E

John A, Ibrahim ZG, Magaji SY, et al. Hepatitis B and C: A Twin Silent Killer. World J Pharma Med Res 2017;3:20–8.

Mohamed AA, Elbedewy TA, El-Serafy M, et al. Hepatitis C virus: A global view. World J Hepatol 2015;7:2676–80. DOI: https://doi.org/10.4254/wjh.v7.i26.2676

Alhetheel AF. Impact of Hepatitis C Virus Infection of Peripheral Blood Mononuclear Cells on the Immune System. Frontiers in Virology 2022;1:45. DOI: https://doi.org/10.3389/fviro.2021.810231

Morozov VA, Lagaye S. Hepatitis C virus: Morphogenesis, infection and therapy. World J Hepatol 2018;10:186–212. DOI: https://doi.org/10.4254/wjh.v10.i2.186

Shiryaev SA, Thomsen ER, Cieplak P, et al. New details of HCV NS3/4A proteinase functionality revealed by a high-throughput cleavage assay. PLoS One 2012;7. DOI: https://doi.org/10.1371/journal.pone.0035759

Pockros PJ. New direct-acting antivirals in the development for hepatitis C virus infection. Therap Adv Gastroenterol 2010;3:191. DOI: https://doi.org/10.1177/1756283X10363055

Yin C, Goonawardane N, Stewart H, Harris M. A role for domain I of the hepatitis C virus NS5A protein in virus assembly. PLoS Pathog 2018;14. DOI: https://doi.org/10.1371/journal.ppat.1006834

O’Boyle DR, Sun JH, Nower PT, et al. Characterizations of HCV NS5A replication complex inhibitors. Virology 2013;444:343–54. DOI: https://doi.org/10.1016/j.virol.2013.06.032

Ferrero DS, Buxaderas M, Rodríguez JF, Verdaguer N. The Structure of the RNA-Dependent RNA Polymerase of a Permutotetravirus Suggests a Link between Primer-Dependent and Primer-Independent Polymerases. PLoS Pathog 2015;11:e1005265. DOI: https://doi.org/10.1371/journal.ppat.1005265

Ahmed A, Felmlee DJ. Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals. Viruses 2015;7(12):6716. DOI: https://doi.org/10.3390/v7122968

Geddawy A, Ibrahim YF, Elbahie NM, Ibrahim MA. Direct Acting Anti-hepatitis C Virus Drugs: Clinical Pharmacology and Future Direction. J Transl Int Med 2017;5:8. DOI: https://doi.org/10.1515/jtim-2017-0007

Chen SL, Yu H, Luo HM, et al. Conservation and sustainable use of medicinal plants: problems, progress, and prospects. Chin Med 2016;11:37. DOI: https://doi.org/10.1186/s13020-016-0108-7

Kingston DGI. Modern natural products drug discovery and its relevance to biodiversity conservation. J Nat Prod 2011;74:496–511. DOI: https://doi.org/10.1021/np100550t

Newman DJ, Cragg GM. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 2012;75:311–35. DOI: https://doi.org/10.1021/np200906s

Atanasov AG, Waltenberger B, Pferschy-Wenzig EM, et al. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnol Adv 2015;33:1582–614. DOI: https://doi.org/10.1016/j.biotechadv.2015.08.001

Harvey AL, Edrada-Ebel R, Quinn RJ. The re-emergence of natural products for drug discovery in the genomics era. Nat Rev Drug Discov 2015;14:111–29. DOI: https://doi.org/10.1038/nrd4510

Abookleesh FL, Al-Anzi BS, Ullah A. Potential Antiviral Action of Alkaloids. Molecules 2022;27:903. DOI: https://doi.org/10.3390/molecules27030903

Wang L, Song J, Liu A, et al. Research Progress of the Antiviral Bioactivities of Natural Flavonoids. Nat Prod Bioprospect 2020;10:271–83. DOI: https://doi.org/10.1007/s13659-020-00257-x

Ahmed S, Ullah N, Parveen S, et al. Effect of Silymarin as an Adjunct Therapy in Combination with Sofosbuvir and Ribavirin in Hepatitis C Patients: A Miniature Clinical Trial. Oxid Med Cell Longev 2022;2022. DOI: https://doi.org/10.1155/2022/9199190

Gu XB, Yang XJ, Hua Z, et al. Effect of oxymatrine on specific cytotoxic T lymphocyte surface programmed death receptor-1 expression in patients with chronic hepatitis B. Chin Med J (Engl) 2012;125:1434–8.

Ferreira MJU. Alkaloids in Future Drug Discovery. Molecules 2022;27. DOI: https://doi.org/10.3390/molecules27041347

Widyawaruyanti A, Tanjung M, Permanasari AA, et al. Alkaloid and benzopyran compounds of Melicope latifolia fruit exhibit anti-hepatitis C virus activities. BMC Complement Med Ther 2021;21. DOI: https://doi.org/10.1186/s12906-021-03202-8

Wang XF, Liu FF, Zhu Z, et al. Flueggenoids A – E, new dinorditerpenoids from Flueggea virosa. Fitoterapia 2019;133:96–101. DOI: https://doi.org/10.1016/j.fitote.2018.12.025

Li XH, Zhang Y, Zhang JH, et al. Myritonines A-C, Alkaloids from Myrioneuron tonkinensis Based on a Novel Hexacyclic Skeleton. J Nat Prod 2016;79:1203–7. DOI: https://doi.org/10.1021/acs.jnatprod.5b01130

Cao MM, Zhang Y, Huang SD, et al. Alkaloids with Different Carbon Units from Myrioneuron faberi. J Nat Prod 2015;78:2609–16. DOI: https://doi.org/10.1021/acs.jnatprod.5b00543

Jardim ACG, Igloi Z, Shimizu JF, et al. Natural compounds isolated from Brazilian plants are potent inhibitors of hepatitis C virus replication in vitro. Antiviral Res 2015;115:39–47. DOI: https://doi.org/10.1016/j.antiviral.2014.12.018

Wahyuni TS, Widyawaruyanti A, Lusida MI. Inhibition of hepatitis C virus replication by chalepin and pseudane IX isolated from Ruta angustifolia leaves. Fitoterapia 2014;99:276–83. DOI: https://doi.org/10.1016/j.fitote.2014.10.011

Cao MM, Zhang Y, Li XH, et al. Cyclohexane-fused octahydroquinolizine alkaloids from Myrioneuron faberi with activity against hepatitis C virus. J Org Chem 2014;79:7945–50. DOI: https://doi.org/10.1021/jo501076x

Huang SD, Zhang Y, Cao MM, et al. Myriberine a, a new alkaloid with an unprecedented heteropentacyclic skeleton from myrioneuron faberi. Org Lett 2013;15:590–3. DOI: https://doi.org/10.1021/ol3034065

Lv XQ, Zou LL, Tan JL, et al. Aloperine inhibits hepatitis C virus entry into cells by disturbing internalisation from endocytosis to the membrane fusion process. Eur J Pharmacol 2020;883. DOI: https://doi.org/10.1016/j.ejphar.2020.173323

Hung TC, Jassey A, Liu CH, et al. Berberine inhibits hepatitis C virus entry by targeting the viral E2 glycoprotein. Phytomedicine 2019;53:62–9. DOI: https://doi.org/10.1016/j.phymed.2018.09.025

Calland N, Dubuisson J, Rouillé Y, Séron K. Hepatitis C virus and natural compounds: A new antiviral approach? Viruses 2012;4:2197–217. DOI: https://doi.org/10.3390/v4102197

Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: An overview. ScientificWorldJournal 2013;2013. DOI: https://doi.org/10.1155/2013/162750

Khan M, Rauf W, Habib F et al. Hesperidin identified from Citrus extracts potently inhibits HCV genotype 3a NS3 protease. BMC Complement Med Ther 2022;22:1–18. DOI: https://doi.org/10.1186/s12906-022-03578-1

Yang L, Lin J, Zhou B, et al. Activity of compounds from Taxillus sutchuenensis as inhibitors of HCV NS3 serine protease. Nat Prod Res 2017;31:487–91. DOI: https://doi.org/10.1080/14786419.2016.1190719

Zhong JD, Feng Y, Li HM, et al. A new flavonoid glycoside from Elsholtzia bodinieri. Nat Prod Res 2016;30:2278–84. DOI: https://doi.org/10.1080/14786419.2016.1164698

Hawas UW, Abou El-Kassem LT, Shaher F, Al-Farawati R. In vitro inhibition of Hepatitis C virus protease and antioxidant by flavonoid glycosides from the Saudi costal plant Sarcocornia fruticosa. Nat Prod Res 2019;33:3364–71. DOI: https://doi.org/10.1080/14786419.2018.1477153

Shimizu JF, Lima CS, Pereira CMH, et al. Flavonoids from Pterogyne nitens Inhibit Hepatitis C Virus Entry. Sci Rep 2017;7. DOI: https://doi.org/10.1038/s41598-017-16336-y

Hawas UW, Abou El-Kassem LT. Thalassiolin D: a new flavone O-glucoside Sulphate from the seagrass Thalassia hemprichii. Nat Prod Res 2017;31:2369–74. DOI: https://doi.org/10.1080/14786419.2017.1308367

Haid S, Novodomská A, Gentzsch J, et al. A plant-derived flavonoid inhibits entry of All HCV genotypes into human hepatocytes. Gastroenterology 2012;143. DOI: https://doi.org/10.1053/j.gastro.2012.03.036

Ciesek S, von Hahn T, Colpitts CC, et al. The green tea polyphenol, epigallocatechin-3-gallate, inhibits hepatitis C virus entry. Hepatology 2011;54:1947–55. DOI: https://doi.org/10.1002/hep.24610

Calland N, Sahuc ME, Belouzard S, et al. Polyphenols Inhibit Hepatitis C Virus Entry by a New Mechanism of Action. J Virol 2015;89:10053–63. DOI: https://doi.org/10.1128/JVI.01473-15

Steinmann J, Buer J, Pietschmann T, Steinmann E. Anti-infective properties of epigallocatechin-3-gallate (EGCG), a component of green tea. Br J Pharmacol 2013;168:1059–73. DOI: https://doi.org/10.1111/bph.12009

Ahmed-Belkacem A, Ahnou N, Barbotte L, et al. Silibinin and Related Compounds Are Direct Inhibitors of Hepatitis C Virus RNA-Dependent RNA Polymerase. Gastroenterology 2010;138:1112–22. DOI: https://doi.org/10.1053/j.gastro.2009.11.053

Fauvelle C, Lambotin M, Heydmann L, et al. A cinnamon-derived procyanidin type A compound inhibits hepatitis C virus cell entry. Hepatol Int. 2017;11:440–5. DOI: https://doi.org/10.1007/s12072-017-9809-y

Blaising J, Lévy PL, Gondeau C, et al. Silibinin inhibits hepatitis C virus entry into hepatocytes by hindering clathrin-dependent trafficking. Cell Microbiol 2013;15:1866–82. DOI: https://doi.org/10.1111/cmi.12155

Rizaldi, G., Hafid, A. F., & Wahyuni, T. S. (2023). Promising alkaloids and flavonoids compounds as anti-hepatitis C virus agents: a review. Journal of Public Health in Africa, 14(s1). https://doi.org/10.4081/jphia.2023.2514

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