Acidul Glycyrrhinic / Glicirhizinic a fost listat printre cele câteva molecule naturale cu potențial de tratament împotriva COVID-19
Unele preparate imunomodulatoare care aduc acid glicirizinic sau sarea lui în cantități optimale pentru a nu avea efecte secundare, pot fi utile în prevenirea COVID-19 dar si a evoluției ei.
GLYCIRRINIC ACID IS LISTED AS A POTENTIAL TREATMENT FOR COVID-19
Glycyrrhinic acid is a molecule with several therapeutic properties obtained from the roots of licorice (Glycyrrhiza sp.), Which has been used as a vegetable with medicinal effects for many years.(1)
This acid has a broad therapeutic function (anti-inflammatory action, antimicrobial and antiviral action, hepatoprotection, among others)(2). Its ability to treat viral infections in humans is one of its most relevant attributes, which has been widely studied for the treatment of a series of viral pathologies.
Currently, there are several studies showing the efficacy and safety of glycyrrhinic acid in the treatment of infections by Epstein-Barr virus (EBV) (3), several types of hepatitis (4-7), human immunodeficiency virus (HIV) (8), herpes (9), human papilloma virus (HPV) (10), among others.
In Brazil, glycyrrhinic acid is commercialized exclusively for the treatment of herpes (labial, genital and zoster) and HPV under the trade name Glizigen® and Viusid®.
The use of glycyrrhinic acid to treat SARS coronavirus.The antiviral capacity of glycyrrhinic acid gained prominence at the beginning of the century with the outbreak of a type of coronavirus (CoV) called SARS-CoV (Severe Acute Respiratory Syndrome - Coronavirus).
During the SARS-CoV epidemic, several molecules were researched to help treating patients. In an in vitro study, glycyrrhinic acid stood out as the most potent SARS-CoV inhibitor with a selectivity index of 67 (6-azauridine, pyrazofurin, mycophenolic acid, ribavirin and glycyrrhinic acid were analysed)(11,12). Later studies showed that derivatives of glycyrrhinic acid have an even more relevant action against SARS-CoV.(13)
Although the 2002-2003 outbreak was a big cause of concern for the population of several countries, the epidemic was well controlled, with no new reports of SARS-CoV since 2004. This reduced the interest in conducting more in-depth clinical studies, therefore, an adequate treatment for SARS-CoV has not yet been identified.
The recent outbreak of a new variation of Coronavirus, named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spreading around the world has brought all the attention to the search for more information about this new pathology (called COVID -19), aiming especially to the development of a vaccine and an effective treatment.
Novel studies have shed light on the SARS-CoV-2 genome. The new coronavirus has some similarities with the old SARS-CoV, sharing about 80% of its nucleotide identity.(14)
Although a 20% difference in nucleotides is considered relevant, this has led scientists to infer that the SARS-CoV infection mechanism may be the same as that of the 2003 virus.
The SARS-causing virus infects lung cells by binding to angiotensin-converting enzyme 2 (ACE2) receptors.(15)
With this in mind, studies were carried out to assess the affinity of the new virus spike protein (S-protein – an important viral portion for its coupling with the target cell) with the ACE2 receptor. Thus, through computer models, it was shown that there is a high affinity of the COVID-19 virus S-protein to this receptor.(16)
The identification of the ACE2 receptor as the potential infection pathway for the SARS-CoV-2 virus, opened the possibility for the emergence of therapies to COVID-19.
Glycyrrhinic acid, a promising molecule to treat COVID-19
A new study from Stanford University in partnership with the University of Hong Kong, released in late January/2020, used a computational model to identify molecules (which were already used for medicinal purposes) that have high affinity for the ACE2 receptor.
The researchers' bet is that molecules, with more affinity to the ACE2 receptor than the virus, can prevent viral infection by competing for the receptor. Due to its high molecular attraction to the ACE2 receptor, glycyrrhinic acid was listed as a potential treatment for COVID-19, along with other promising molecules.(17)
The study highlighted the anti-SARS-CoV ability that glycyrrhinic acid shown in previous research (decreased viral absorption and penetration in its presence).(11)
New studies need to be carried out to confirm whether glycyrrhinic acid can be effective as a treatment for the COVID-19 disease, however this molecule stands out as being a highly promising therapy.
Catalysis Espana - Sientific Departament
1. Blumenthal M, Goldberg A, Brinckmann J. 2000. Herbal Medicine: Expanded Commission E Monographs. American Botanical Council: Newton, 233–236.
2. Marjan Nassiri Asl Hossein Hosseinzadeh. 2008. Phytotherapy Research. Review of Pharmacological Effects of Glycyrrhiza sp. and its Bioactive Compounds. Pages 709-724.
3. Lin JC. 2003. Mechanism of action of glycyrrhizic acid in inhibition of Epstein-Barr virus replication in vitro. Antiviral Res 59: 41–47.
4. Crance JM, Biziagos E, Passagot J, Van Cuyck-Gandre H, Deloince R. 1990. Inhibition of hepatitis A virus replication in vitro by antiviral compounds. J Med Virol 31: 155–160.
5. Takahara T, Watanabe A, Shiraki K. 1994. Effects of glycyrrhizin on hepatitis B surface antigen: a biochemical and morphological study. J Hepatol 21: 601–609.
6. Sato H, Goto W, Yamamura J et al. 1996. Therapeutic basis of glycyrrhizin on chronic hepatitis B. Antiviral Res 30: 171– 177.
7. Van Rossum TGJ, Vulto AG, De Man RA, Brouwer JT, Schalam SW. 1998. Review article: Glycyrrhizin as a potential treatment for chronic hepatitis C. Aliment Pharmacol Ther 12: 199–205.
8. Ito M, Sato A, Hirabayashi K et al. 1988. Mechanism of inhibitory effect of glycyrrhizin on replication of human immunodeficiency virus (HIV). Antiviral Res 10: 289–298.
9. Vick FR, Hidalgo LH, Zenón MC, Martínez S. 2000. Uso tópico del ácido glicirricínico en el herpes genital Rev Hosp M Gea Glz.
10. Cárdenas J. A. E. M., Álvarez A., Gutiérrez M. C., Infante L. A. B. D. 2005. Eficacia clínica y endoscopica del ácido glicirrínico activado (Epigen®) en el tratamiento de la infeccion por el virus del papiloma humano em el cuello uterino. Revista del Climatério, V 8.
11. J Cinatl, B Morgenstern, G Bauer, P Chandra, H Rabenau, H W Doerr. 2003. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet; 361: 2045–46.
12. Cinatl, J., Jr., 2005. Antiviral activity of glycyrrhizic acid derivatives against SARS-coronavirus. J Med Chem 48(4), 1256-1259.
13. Gerold Hoever, Lidia Baltina, Martin Michaelis, Rimma Kondratenko, Lia Baltina, Genrich A. Tolstikov, Hans W. Doerr, and Jindrich Cinatl, Jr. 2004. Antiviral Activity of Glycyrrhizic Acid Derivatives against SARS-Coronavirus. J. Med. Chem. 48, 1256-1259
14. Lisa E. Gralinski 1 andVineet D. Menachery. 2020. Return of the Coronavirus: 2019-nCoV. Viruses, 12(2), 135
15. Kuba K1, Imai Y, Rao S, Gao H, Guo F, Guan B, Huan Y, Yang P, Zhang Y, Deng W, Bao L, Zhang B, Liu G, Wang Z, Chappell M, Liu Y, Zheng D, Leibbrandt A, Wada T, Slutsky AS, Liu D, Qin C, Jiang C, Penninger JM. 2005. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. Aug;11(8):875-9. Epub 2005 Jul 10.
16. Xu, X., Chen, P., Wang, J., Feng, J., Zhou, H., Li, X., ... & Hao, P. 2020. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Science China Life Sciences, 1-4.
17. Chen, H.; Du, Q. 2020. Potential Natural Compounds for Preventing SARS-CoV-2 (2019-nCoV) Infection. Preprints, 2020010358