Natural products and their derivatives against the Ebola virus

Authors

Keywords:

antiviral agents, ebolavirus, hemorrhagic fever, ebola, medicine traditional, plants medicinal.

Abstract

Background: Ebola is a virus that causes hemorrhagic fever, which has a high mortality rate and is therefore considered a public health problem and a bioterrorist agent. Although several therapeutic strategies have now been developed, the problem lies in the need to generate a long-lasting, cross-species immune response against multiple species of the virus. Natural compounds are a valuable and important source of chemical diversity including antiviral activity and may be useful as prophylactic and/or therapeutic agents against Ebola virus infections.

Objective: The objective of the review was to highlight the beneficial effects of plants as well as their bioactive compounds for the possible treatment of Ebola hemorrhagic fever.

Methods: The methodology consisted of a bibliometric search and analysis in four databases PubMed, Web of Science, Scopus and Cochrane Library using the descriptors: "traditional medicine", "medicinal plants", "herbs", "phytochemicals", "herbal medicine", "hemorrhagic fever" and "Ebolavirus" and the search equation was adjusted in each of them.

Results: We obtained 293 research articles from which 20 articles were selected for critical analysis. The compounds acted through different mechanisms of action such as inhibition of viral proteins as well as interference in the different phases of the viral infection cycle.

Conclusions: Most of the compounds that showed promising effect for inhibition of infection by this virus include polar molecules such as: BanLec H84T, eugenol, ellagic acid, gallic acid, myricetin, curcumin, emodin, silvestrol resveratrol and 18β- glycyrrhetinic acid.

Downloads

Download data is not yet available.

Author Biography

Marco Orlando Fuel Herrera, Universidad de Granada

Instituto de Biopatología y Medicina Regenerativa (IBIMER). Investigador

References

1. Baseler L, Chertow DS, Johnson KM, Feldmann H, Morens DM. The pathogenesis of ebola virus disease. Annu Rev Pathol Mech Dis. 2017;12:387-418. DOI: https://doi.org/10.1146/annurev-pathol-052016-100506

2. Kett M, Cole E, Beato L, Carew M, Ngafuan R, Konneh F, et al. The ebola crisis and people with disabilities’ access to healthcare and government services in Liberia. Int J Equity Health. 2021;20(1):247. DOI: https://doi.org/10.1186/s12939-021-01580-6

3. Organización Mundial de la Salud (OMS). Detectado un nuevo brote de ebola en el noroeste de la República Democrática del Congo. El equipo OMS de refuerzo apoya la respuesta. 2020 [acceso 04/03/2021]. Disponible en: https://www.who.int/es/news/item/01-06-2020-new-ebola-outbreak-detected-in-northwest-democratic-republic-of-the-congo-who-surge-team-supporting-the-response

4. Dhama K, Karthik K, Khandia R, Chakraborty S, Munjal A, Latheef S, et al. Advances in designing and developing vaccines, drugs, and therapies to counter ebola virus. Front Immunol. 2018;9:1803. DOI: https://doi.org/10.3389/fimmu.2018.01803

5. Hoenen T, Groseth A, Feldmann H. Therapeutic strategies to target the ebola virus life cycle. Nat Rev Microbiol. 2019;17(10):593-606. DOI: https://doi.org/10.1038/s41579-019-0233-2

6. Sissoko D, Duraffour S, Kerber R, Kolie JS, Beavogui AH, et al. Persistence and clearance of Ebola virus RNA from seminal fluid of ebola virus disease survivors: a longitudinal analysis and modelling study. Lancet Glob Heal. 2017;5(1):e80-8. DOI: https://doi.org/10.1016/s2214-109x(16)30243-1

7. O’Donnell KL, Marzi A. Immunotherapeutics for ebola virus disease: Hope on the Horizon. Biol Targets Ther. 2021;15:79-86. DOI: https://doi.org/10.2147/btt.s259069

8. de la Torre BG, Albericio F. The pharmaceutical industry in 2020. An analysis of FDA drug approvals from the perspective of molecules. Molecules. 2021;26(3):627. DOI: https://doi.org/10.3390/molecules26030627

9. Ramos JM, González-Alcaide G, Gutiérrez F. Análisis bibliométrico de la producción científica española en Enfermedades Infecciosas y en Microbiología. Enferm Infecc Microbiol Clin. 2016;34(3):166-76. DOI: https://doi.org/10.1016/j.eimc.2015.04.007

10. Ao Z, Wang L, Azizi H, Olukitibi TA, Kobinger G, Yao X. Development and evaluation of an ebola virus glycoprotein mucin-like domain replacement system as a new dendritic cell-targeting vaccine approach against HIV-1. J Virol. 2021;95(15):e0236820. DOI: https://doi.org/10.1128/jvi.02368-20

11. Cui Q, Cheng H, Xiong R, Zhang G, Du R, Anantpadma M, et al. Identification of diaryl-quinoline compounds as entry inhibitors of ebola virus. Viruses. 2018;10(12):678. DOI: https://doi.org/10.3390/v10120678

12. Shaikh F, Zhao Y, Alvarez L, Iliopoulou M, Lohans C, Schofield C, et al. Structure-based in silico screening identifies a potent ebolavirus inhibitor from a traditional chinese medicine library. J Med Chem. 2019;62(6):2928-37. DOI: https://doi.org/10.1021/acs.jmedchem.8b01328

13. Kuo YT, Liu CH, Corona A, Fanunza E, Tramontano E, Lin LT. The methanolic extract of perilla frutescens robustly restricts ebola virus glycoprotein-mediated entry. Viruses. 2021;13(9):1793. DOI: https://doi.org/10.3390/v13091793

14. Jain S, Martynova E, Rizvanov A, Khaiboullina S, Baranwal M. Structural and functional aspects of ebola virus proteins. Pathogens. 2021;10(10):1330. DOI: https://doi.org/10.3390/pathogens10101330

15. Wang Z, Liang H, Cao H, Zhang B, Li J, Wang W, et al. Efficient ligand discovery from natural herbs by integrating virtual screening, affinity mass spectrometry and targeted metabolomics. Analyst. 2019;144(9):2881-90. DOI: https://doi.org/10.1039/c8an02482k

16. Lija-Escaline J, Senthil-Nathan S, Thanigaivel A, Pradeepa V, Vasantha-Srinivasan P, Ponsankar A, et al. Physiological and biochemical effects of botanical extract from Piper nigrum Linn (Piperaceae) against the dengue vector Aedes aegypti Liston (Diptera: Culicidae). Parasitol Res. 2015;114(11):4239-49. DOI: https://doi.org/10.1007/s00436-015-4662-1

17. Fu X, Wang Z, Li L, Dong S, Li Z, Jiang Z, et al. Novel chemical ligands to ebola virus and marburg virus nucleoproteins identified by combining affinity mass spectrometry and metabolomics approaches. Sci Rep. 2016;6(1):1-13. DOI: https://doi.org/10.1038/srep29680

18. van de Sand L, Bormann M, Alt M, Schipper L, Silke C, Steinmann E, et al. Glycyrrhizin effectively inhibits SARS-CoV-2 replication by inhibiting the viral main protease. Viruses. 2021;13(4):609. DOI: https://doi.org/10.3390/v13040609

19. Liang SB, Hou WB, Zheng RX, Liang CH, Yan LJ, Wang HN, et al. Compound glycyrrhizin injection for improving liver function in children with acute icteric hepatitis: A systematic review and meta-analysis. Integr Med Res. 2022;11(1):100772. DOI: https://doi.org/10.1016/j.imr.2021.100772

20. Huan C, Xu Y, Zhang W, Guo T, Pan H, Gao S. Research progress on the antiviral activity of glycyrrhizin and its derivatives in liquorice. Front Pharmacol. 2021;12:680674. DOI: https://doi.org/10.3389/fphar.2021.680674

21. Nasution MAF, Toepak EP, Alkaff AH, Tambunan USF. Flexible docking-based molecular dynamics simulation of natural product compounds and ebola virus nucleocapsid (EBOV NP): A computational approach to discover new drug for combating ebola. BMC Bioinformatics. 2018;19(suppl 14):419. DOI: https://doi.org/10.1186/s12859-018-2387-8

22. Kasajima N, Matsuno K, Miyamoto H, Kajihara M, Igarashi M, Takada A. Functional importance of hydrophobic patches on the ebola virus VP35 IFN-inhibitory domain. Viruses. 2021;13(11):2316. DOI: https://doi.org/10.3390/v13112316

23. Cantoni D, Rossman JS. Ebolaviruses: New roles for old proteins. PLoS Negl Trop Dis. 2018;12(5):e0006349. DOI: https://doi.org/10.1371/journal.pntd.0006349

24. Setlur AS, Naik SY, Skariyachan S. Herbal lead as ideal bioactive compounds against probable drug targets of ebola virus in comparison with known chemical analogue: a computational drug discovery perspective. Interdiscip Sci. 2017;9(2):254-77. DOI: https://doi.org/10.1007/s12539-016-0149-8

25. Baikerikar S. Curcumin and natural derivatives inhibit ebola viral proteins: An In silico approach. Pharmacognosy Res. 2017;9(suppl 1):S15-22. DOI: https://doi.org/10.4103/pr.pr_30_17

26. Mounce BC, Cesaro T, Carrau L, Vallet T, Vignuzzi M. Curcumin inhibits zika and chikungunya virus infection by inhibiting cell binding. Antiviral Res. 2017;142:148-57. DOI: https://doi.org/10.1016/j.antiviral.2017.03.014

27. Kwofie SK, Broni E, Teye J, Quansah E, Issah I, Wilson MD, et al. Pharmacoinformatics-based identification of potential bioactive compounds against Ebola virus protein VP24. Comput Biol Med. 2019;113:103414. DOI: https://doi.org/10.1016/j.compbiomed.2019.103414

28. Daino GL, Frau A, Sanna C, Rigano D, Distinto S, Madau V, et al. Identification of myricetin as an ebola virus VP35-Double-Stranded RNA interaction inhibitor through a novel fluorescence-based assay. Biochemistry. 2018;57(44):6367-78. DOI: https://doi.org/10.1021/acs.biochem.8b00892

29. Ghassemi-Rad J, Maleki M, Knickle AF, Hoskin DW. Myricetin-induced oxidative stress suppresses murine T lymphocyte activation. Cell Biol Int. 2018;42(8):1069-75. DOI: https://doi.org/10.1002/cbin.10977

30. Ren JX, Zhang RT, Zhang H, Cao XS, Liu LK, Xie Y. Identification of novel VP35 inhibitors: Virtual screening driven new scaffolds. Biomed Pharmacother. 2016;84:199-207. DOI: https://doi.org/10.1016/j.biopha.2016.09.034

31. Karthick V, Nagasundaram N, Priya CG, Chakraborty C, Siva R, Lu A, et al. Virtual screening of the inhibitors targeting at the viral protein 40 of ebola virus. Infect Dis Poverty. 2016;5(1):12. DOI: https://doi.org/10.1186/s40249-016-0105-1

32. Mirza MU, Ikram N. Integrated computational approach for virtual hit identification against ebola viral proteins VP35 and VP40. Int J Mol Sci. 2016;17(11):1748. DOI: https://doi.org/10.3390/ijms17111748

33. Mitchell CA, Ramessar K, O’Keefe BR. Antiviral lectins: Selective inhibitors of viral entry. Antiviral Res. 2017;142:37-54. DOI: https://doi.org/10.1016/j.antiviral.2017.03.007

34. Degroote RL, Korbonits L, Stetter F, Kleinwort K, Schilloks MC, Amann B, et al. Banana lectin from musa paradisiaca is mitogenic for cow and pig PBMC via IL-2 pathway and ELF1. Immuno. 2021;1(3):264-76. DOI: https://doi.org/10.3390/immuno1030018

35. Covés-Datson EM, Dyall J, DeWald LE, King S, Dube D, Legendre M, et al. Inhibition of ebola virus by a molecularly engineered banana lectin. PLoS Negl Trop Dis. 2019;13(7):e0007595. DOI: https://doi.org/10.1371/journal.pntd.0007595

36. Taleuzzaman M, Jain P, Verma R, Iqbal Z, Mirza MA. Eugenol as a potential drug candidate: a review. Curr Top Med Chem. 2021;21(20):1804-15. DOI: https://doi.org/10.2174/1568026621666210701141433

37. Lane T, Anantpadma M, Freundlich JS, Davey RA, Madrid PB, Ekins S. The natural product eugenol is an inhibitor of the ebola virus in vitro. Pharm Res. 2019;36(7):1-6. DOI: https://doi.org/10.1007/s11095-019-2629-0

38. Cui Q, Du R, Anantpadma M, Schafer A, Hou L, Tian J, et al. Identification of ellagic acid from plant rhodiola rosea L. as an anti-ebola virus entry inhibitor. Viruses. 2018;10(4):152. DOI: https://doi.org/10.3390/v10040152

39. Yang Y, Cheng H, Yan H, Wang PZ, Rong R, Zhang YY, et al. A cell-based high-throughput protocol to screen entry inhibitors of highly pathogenic viruses with traditional chinese medicines. J Med Virol. 2017;89(5):908-16. DOI: https://doi.org/10.1002/jmv.24705

40. Oh C, Price J, Brindley MA, Widrlechner MP, Qu L, McCoy JA, et al. Inhibition of HIV-1 infection by aqueous extracts of Prunella vulgaris L. Virol J. 2011;8:188. DOI: https://doi.org/10.1186/1743-422x-8-188

41. Zhang X, Ao Z, Bello A, Ran X, Liu S, Wigle J, et al. Characterization of the inhibitory effect of an extract of Prunella vulgaris on Ebola virus glycoprotein (GP)-mediated virus entry and infection. Antiviral Res. 2016;127:20-31. DOI: https://doi.org/10.1016/j.antiviral.2016.01.001

42. Luthra P, Liang J, Pietzsch CA, Khadka S, Edwards MR, Wei S, et al. A high throughput screen identifies benzoquinoline compounds as inhibitors of Ebola virus replication. Antiviral Res. 2018;150:193-201. DOI: https://doi.org/10.1016/j.antiviral.2017.12.019

43. Fuel M, Cangui S. El silvestrol como agente antiviral de amplio espectro. Rev Bas

Cienc. 2021;6(2):41-56. DOI: https://doi.org/10.33936/rev_bas_de_la_ciencia.v6i2.2814

44. Biedenkopf N, Lange-Grünweller K, Schulte FW, Weiβer A, Müller C, Becker D, et al. The natural compound silvestrol is a potent inhibitor of Ebola virus replication. Antiviral Res. 2017;137:76-81. DOI: https://doi.org/10.1016/j.antiviral.2016.11.011

45. Sizikova TE, Borisevlch GV, Shcheblyakov DV, Burmistrova DA, Lebedev VN. The use of monoclonal antibodies for the treatment of ebola virus disease. Vopr Virusol. 2018;63(6):245-9. DOI: https://doi.org/10.18821/0507-4088-2018-63-6-245-249

Downloads

Published

2024-11-15

How to Cite

1.
Fuel Herrera MO, Cangui-Panchi SP. Natural products and their derivatives against the Ebola virus. Rev Cubana Inv Bioméd [Internet]. 2024 Nov. 15 [cited 2025 Jul. 26];43. Available from: https://revibiomedica.sld.cu/index.php/ibi/article/view/2325

Issue

Section

ARTÍCULOS DE REVISIÓN