Peranan Akar Manis (Glycyrrhiza sp.) sebagai Terapi Alternatif Antivirus  pada COVID-19

Berlianti Bulovannelisa Meykward Salamahu; Wani Devita Gunardi; Eva Oktavia

doi:10.36452/jkdoktmeditek.v28i3.2511

Authors

Berlianti Bulovannelisa Meykward Salamahu Fakultas Kedokteran dan Ilmu Kesehatan, Universitas Kristen Krida Wacana, Jakarta, Indonesia
Wani Devita Gunardi Departemen Mikrobiologi, Fakultas Kedokteran dan Ilmu Kesehatan, Universitas Kristen Krida Wacana, Jakarta, Indonesia
Eva Oktavia Departemen Anestesi, Fakultas Kedokteran dan Ilmu Kesehatan, Universitas Kristen Krida Wacana, Jakarta, Indonesia

DOI:

https://doi.org/10.36452/jkdoktmeditek.v28i3.2511

Keywords:

akar manis, anti-inflamasi, antivirus, imunomodulasi, SARS-CoV, virus influenza

Abstract

Coronavirus disease 2019 (COVID-19) yang diakibatkan oleh infeksi severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) merupakan masalah kesehatan global yang memengaruhi seluruh lapisan masyarakat dan berdampak buruk pada kesejahteraan manusia. Hingga saat ini, belum ditemukan terapi spesifik terhadap SARS-CoV-2 sehingga diperlukan agen terapeutik alternatif yang dapat mencegah maupun mengobati penyakit ini. Tanaman akar manis merupakan salah satu tanaman herbal yang telah menunjukkan kemampuan signifikan dalam menghambat replikasi SARS-CoV-1 sehingga memiliki potensi dalam terapi COVID-19. Dalam tinjauan pustaka ini, dilakukan analisis literatur menggunakan pangkalan data Pubmed guna mengetahui efek senyawa akar manis (Glycyrrhiza sp.) sebagai antivirus, anti-inflamasi, dan imunomodulator yang dapat digunakan sebagai terapi alternatif pada penyakit COVID-19. Dari data yang didapatkan, ditemukan bahwa glycyrrhizin merupakan senyawa dengan mekanisme kerja paling luas pada beragam target protein SARS-CoV-2 dan dapat menghambat replikasi virus ini pada konsentrasi 0,5 mg/ml secara in vitro. Secara khusus, glycyrrhizin mampu bekerja pada 3CLpro, suatu target protein yang konsisten ditemukan pada strain virus SARS-CoV-2 sehingga menghindari resistensi akibat mutasi. Hasil tinjauan pustaka ini menunjukkan adanya peranan akar manis (Glycyrrhiza sp.) sebagai terapi alternatif antivirus pada COVID-19 melalui kerjanya secara langsung pada SARS-CoV-2 serta didukung oleh efek anti-inflamasi dan imunomodulasi yang signifikan.

References

Adhikari SP, Meng S, Wu Y, Mao Y, Ye R, Wang Q, et al. A scoping review of 2019 novel coronavirus during the early outbreak period: Epidemiology, causes, clinical manifestation and diagnosis, prevention and control. 2020;1–12.

Kemenkes RI. Pedoman pencegahan dan pengendalian corona virus disease (Covid-19). Direktorat Jenderal Pencegah dan Pengendali Penyakit. 2020;135.

WHO. Statement on the second meeting of the international health regulations emergency committee regarding the outbreak of novel coronavirus (2019-nCoV). 2020.

Kementerian Kesehatan Republik Indonesia. Situasi terkini perkembangan coronavirus disease (COVID-19) 25 Maret 2021 [Internet]. 2021. Available from: https://infeksiemerging.kemkes.go.id/situasi-infeksi-emerging/situasi-terkini-perkembangan-coronavirus-disease-covid-19-25-maret-2021

Regan H. Confidence in Chinese vaccines has taken a hit. But as coronavirus cases grow, some countries are still pushing ahead [Internet]. CNN. 2021 [cited 2021 Mar 27]. Available from: https://edition.cnn.com/2021/01/17/asia/sinovac-vaccine-asia-efficacy-intl-hnk/index.html

Salehi B, Konovalov DA, Fru P, Kapewangolo P, Peron G, Ksenija MS, et al. Areca catechu —from farm to food and biomedical applications. Phyther Res [Internet]. 2020 Sep 11;34(9):2140–58. Available from: https://onlinelibrary.wiley.com/doi/10.1002/ptr.6665

Salehi B, Zakaria ZA, Gyawali R, Ibrahim SA, Rajkovic J, Shinwari ZK, et al. Piper species: A comprehensive review on their phytochemistry, biological activities and applications. Molecules [Internet]. 2019 Apr 7;24(7):1364. Available from: https://www.mdpi.com/1420-3049/24/7/1364

Kao T, Wu C, Yen G. Bioactivity and potential health benefits of licorice. J. Agric. Food Chem. 2014, 62(3):542–53.

Yang F, Zhang Y, Tariq A, Jiang X, Ahmed Z, Zhihao Z, et al. Food as medicine: A possible preventive measure against coronavirus disease (COVID-19). Phytother Res. 2020;34(12):3124–36.

Yang R, Wang LQ, Yuan BC, Liu Y. The Pharmacological activities of licorice. Planta Med. 2015;81(18):1654–69.

Wang L, Yang R, Yuan B, Liu Y, Liu C. The antiviral and antimicrobial activities of licorice, a widely-used Chinese herb. Acta Pharm Sin B [Internet]. 2015;5(4):310–5. Available from: http://dx.doi.org/10.1016/j.apsb.2015.05.005

Dao TT, Nguyen PH, Lee HS, Kim E, Park J, Lim S Il, et al. Chalcones as novel influenza A (H1N1) neuraminidase inhibitors from Glycyrrhiza inflata. Bioorganic Med Chem Lett [Internet]. 2011;21(1):294–8. Available from: http://dx.doi.org/10.1016/j.bmcl.2010.11.016

Fu XX, Du LL, Zhao N, Dong Q, Liao YH, Du YM. 18β-Glycyrrhetinic acid potently inhibits Kv1.3 potassium channels and T cell activation in human Jurkat T cells. J Ethnopharmacol. 2013;148(2):647–54.

Chu X, Jiang L, Wei M, Yang X, Guan M, Xie X, et al. Attenuation of allergic airway inflammation in a murine model of asthma by Licochalcone A. Immunopharmacol Immunotoxicol. 2013;35(6):653–61.

Yang N, Patil S, Zhuge J, Wen MC, Bolleddula J, Doddaga S, et al. Glycyrrhiza uralensis flavonoids present in anti-asthma formula, ASHMITM, inhibit memory Th2 responses in vitro and in vivo. Phyther Res. 2013;27(9):1381–91.

Fu Y, Zhou H, Wang S, Wei Q. Glycyrol suppresses collagen-induced arthritis by regulating autoimmune and inflammatory responses. PLoS One. 2014;9(7):1–9.

Li P, Li Y, Jiang H, Xu Y, Liu X, Che B, et al. Glabridin, an isoflavan from licorice root, ameliorates imiquimod-induced psoriasis-like inflammation of BALB/c mice. Int Immunopharmacol [Internet]. 2018;59(April):243–51. Available from: https://doi.org/10.1016/j.intimp.2018.04.018

Wang Y, Zhang Y, Peng G, Han X. Glycyrrhizin ameliorates atopic dermatitis-like symptoms through inhibition of HMGB1. Int Immunopharmacol [Internet]. 2018;60:9–17. Available from: https://doi.org/10.1016/j.intimp.2018.04.029

Yang EJ, Song IS, Song KS. Ethanol extract of Glycyrrhizae radix modulates the responses of antigen-specific splenocytes in experimental autoimmune encephalomyelitis. Phytomedicine [Internet]. 2019;54:56–65. Available from: https://doi.org/10.1016/j.phymed.2018.09.189

Vardhan S, Sahoo SK. In silico ADMET and molecular docking study on searching potential inhibitors from limonoids and triterpenoids for COVID-19. Comput Biol Med [Internet]. 2020;124:103936. Available from: https://www.ncbi.nlm.nih.gov/pubmed/32738628

Sinha SK, Prasad SK, Islam MA, Gurav SS, Patil RB, AlFaris NA, et al. Identification of bioactive compounds from Glycyrrhiza glabra as possible inhibitor of SARS-CoV-2 spike glycoprotein and non-structural protein-15: a pharmacoinformatics study. J Biomol Struct Dyn [Internet]. 2020;0(0):1–15. Available from: https://doi.org/10.1080/07391102.2020.1779132

Hejazi II, Beg MA, Imam MA, Athar F, Islam A. Glossary of phytoconstituents: Can these be repurposed against SARS CoV-2? A quick in silico screening of various phytoconstituents from plant Glycyrrhiza glabra with SARS CoV-2 main protease. Food Chem Toxicol [Internet]. 2021 Apr;150(January):112057. Available from: http://www.ncbi.nlm.nih.gov/pubmed/33592201

Aishwarya S, Gunasekaran K, Sagaya Jansi R, Sangeetha G. From genomes to molecular dynamics - A bottom up approach in extrication of SARS CoV-2 main protease inhibitors. Comput Toxicol (Amsterdam, Netherlands) [Internet]. 2021 May;18:100156. Available from: http://www.ncbi.nlm.nih.gov/pubmed/33532671

Van de Sand L, Bormann M, Alt M, Schipper L, Heilingloh CS, Todt D, et al. Glycyrrhizin effectively neutralizes SARS-CoV-2 in vitro by inhibiting the viral main protease. bioRxiv. 2020;1–10.

Tan Q, Duan L, Ma Y, Wu F, Huang Q, Mao K, et al. Is oseltamivir suitable for fighting against COVID-19: In silico assessment, in vitro and retrospective study. Bioorg Chem [Internet]. 2020;104(January):104257. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32927129

Michaelis M, Geiler J, Naczk P, Sithisarn P, Leutz A, Doerr HW, et al. Glycyrrhizin exerts antioxidative effects in H5N1 influenza A virus-infected cells and inhibits virus replication and pro-inflammatory gene expression. PLoS One. 2011;6(5).

Cheke RS, Narkhede RR, Shinde SD, Ambhore JP, Jain PG. Natural product emerging as potential sars spike glycoproteins-ace2 inhibitors to combat COVID-19 attributed by in-silico investigations. Biointerface Res Appl Chem. 2021;11(3):10628–39.

Wang Y, Zhang Y, Peng G, Han X. Glycyrrhizin ameliorates atopic dermatitis-like symptoms through inhibition of HMGB1. Int Immunopharmacol [Internet]. 2018;60(January):9–17. Available from: https://doi.org/10.1016/j.intimp.2018.04.029

Bailly C, Vergoten G. Glycyrrhizin: An alternative drug for the treatment of COVID-19 infection and the associated respiratory syndrome? Pharmacol Ther [Internet]. 2020;214:107618. Available from: https://doi.org/10.1016/j.pharmthera.2020.107618

Luo P, Liu D, Li J. Pharmacological perspective: glycyrrhizin may be an efficacious therapeutic agent for COVID-19. Int J Antimicrob Agents [Internet]. 2020;55(6):105995. Available from: https://doi.org/10.1016/j.ijantimicag.2020.105995

Murck H. Symptomatic protective action of Glycyrrhizin (Licorice) in COVID-19 infection? Front Immunol. 2020;11(May):1–5.

Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Vol. 39, Seminars in Immunopathology. Springer Verlag; 2017. p. 529–39.

Ali A, Badawy MEI, Shah R, Rehman W, El Y. Synthesis, characterization and in-silico ADMET screening of mono- and di-hydrazides and hydrazones. Pelagia Res Libr Der [Internet]. 2017;8(4):446–60. Available from: www.pelagiaresearchlibrary.com

Jean-Quartier C, Jeanquartier F, Jurisica I, Holzinger A. In silico cancer research towards 3R. BMC Cancer. 2018;18(1):1–12.

FDA. FDA approves first treatment for COVID-19 | FDA [Internet]. 2020 [cited 2021 Aug 30]. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-covid-19

Kokic G, Hillen HS, Tegunov D, Dienemann C, Seitz F, Schmitzova J, et al. Mechanism of SARS-CoV-2 polymerase stalling by remdesivir. Nat Commun 2021 121 [Internet]. 2021 Jan 12 [cited 2021 Aug 30];12(1):1–7. Available from: https://www.nature.com/articles/s41467-020-20542-0