Potential of Emodin as Effective Therapy Overcoming COVID-19 Through Inhibition of the SARS-CoV-2 Spike Protein Interaction on ACE2 Receptors
DOI:
https://doi.org/10.36497/jri.v44i4.355Keywords:
ACE2 receptor, COVID-19, emodin, SARS-CoV-2, spike proteinAbstract
Background: The coronavirus disease 2019 (COVID-19) once became a major pandemic in the history of human health. Patients in severe to critical conditions, especially with comorbidities, are more likely to have complications such as ARDS, cytokine storm, higher mortality rates, and require more effective treatments. Emodin is a candidate regimen that has the potential benefit for COVID-19.
Method: This literature review was synthesized with literature searches on journal databases such as PubMed, ScienceDirect, EMBASE, and the Google Scholar search engine. As a result, three main articles and 36 supporting articles were used to synthesize this literature review.
Results: The pathogenesis of SARS-CoV-2 infection was similar to SARS-CoV infection, as demonstrated by Hoffmann et al, namely through the interaction of viral spike (S) protein with ACE2 receptors in the human body, so the inhibition of this interaction would be one of the therapeutic targets. Ho et al proved that emodin can inhibit the binding of the SARS-CoV S protein to ACE2 in vitro. The direct inhibition of S protein may also support the ACE2 cardioprotective function in patients with cardiovascular comorbidities. Emodin is also superior because it has various other benefits such as anti-inflammatory and immunosuppressive activity. Based on the research of Dong et al, emodin can be given orally but in combination with inhibitors of glucuronidation, metabolism can increase the bioavailability of this drug.
Conclusion: Emodin has the potential to be developed for the effective therapy of COVID-19.
Downloads
References
Handayani D, Hadi DR, Isbaniah F, Burhan E, Agustin H. Penyakit Virus Corona 2019. Jurnal Respirologi Indonesias. 2020;40(2):119–29.
Susilo A, Rumende CM, Pitoyo WC, Santoso WD, Yulianti M, Herikurniawan, et al. Coronavirus disease 2019: Review of current literatures. Jurnal Penyakit Dalam Indonesia. 2020;7(1):45–67.
World Health Organization. WHO COVID-19 dashboard [Internet]. 2020 [cited 2020 Aug 3]. Available from: https://data.who.int/dashboards/covid19/cases?n=c
Satuan Tugas Penanganan COVID-19. Peta sebaran COVID-19 [Internet]. Satuan Tugas Penanganan COVID-19. 2020 [cited 2020 Aug 3]. Available from: https://covid19.go.id/id
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506.
Guan W jie, Ni Z yi, Hu Y, Liang W hua, Ou C quan, He J xing, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. New England Journal of Medicine. 2020;382(18):1708–20.
Zhou C, Gao C, Xie Y, Xu M. COVID-19 with spontaneous pneumomediastinum. Lancet Infect Dis. 2020;20(4):510.
Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020;46(4):586–90.
Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Anal. 2020;10(2):102–8.
Guo J, Huang Z, Lin L, Lv J. Coronavirus disease 2019 (Covid-19) and cardiovascular disease: A viewpoint on the potential influence of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers on onset and severity of severe acute respiratory syndrome coronavirus 2 infection. J Am Heart Assoc. 2020;9(7):e016219.
Ho TY, Wu SL, Chen JC, Li CC, Hsiang CY. Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction. Antiviral Res. 2007;74(2):92–101.
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. New England Journal of Medicine. 2020;382(8):727–33.
Zhou P, Yang X Lou, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270–3.
National Center for Biotechnology Information. Emodin [Internet]. 2004 [cited 2020 May 13]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Emodin
Zhang B, Qi F. Herbal medicines exhibit a high affinity for ACE2 in treating COVID-19. Biosci Trends. 2023;17(1):14–20.
Nejat R, Torshizi MF, Najafi DJ. S protein, ACE2 and host cell proteases in SARS-CoV-2 cell entry and infectivity; Is soluble ACE2 a two blade sword? A narrative review. Vaccines (Basel). 2023;11(2):204.
Li JJ, Li YX, Li N, Zhu HT, Wang D, Zhang YJ. The genus Rumex (Polygonaceae): An ethnobotanical, phytochemical and pharmacological review. Nat Prod Bioprospect. 2022;12(1):21.
Kuo IP, Lee PT, Nan FH. Rheum officinale extract promotes the innate immunity of orange-spotted grouper (Epinephelus coioides) and exerts strong bactericidal activity against six aquatic pathogens. Fish Shellfish Immunol. 2020;102:117–24.
Naz S, Imran M, Rauf A, Orhan IE, Shariati MA, Iahtisham-Ul-Haq, et al. Chrysin: Pharmacological and therapeutic properties. Life Sci. 2019;235:116797.
Ma L le, Liu H min, Liu X mei, Yuan X yu, Xu C, Wang F, et al. Screening S protein – ACE2 blockers from natural products: Strategies and advances in the discovery of potential inhibitors of COVID-19. Eur J Med Chem. 2021;226:113857.
de Oliveira PG, Termini L, Durigon EL, Lepique AP, Sposito AC, Boccardo E. Diacerein: A potential multi-target therapeutic drug for COVID-19. Med Hypotheses. 2020;144:109920.
Muchtaridi M, Fauzi M, Ikram NKK, Gazzali AM, Wahab HA. Natural flavonoids as potential angiotensin-converting enzyme 2 inhibitors for Anti-SARS-CoV-2. Molecules. 2020;25(17):3980.
Dong X, Zeng Y, Liu Y, You L, Yin X, Fu J, et al. Aloe-emodin: A review of its pharmacology, toxicity, and pharmacokinetics. Phytotherapy Research. 2020;34(2):1207–18.
Stompor–gorący M. The health benefits of emodin, a natural anthraquinone derived from rhubarb—a summary update. Int J Mol Sci. 2021;22(17):9522.
Chen Y, Zhang T, Wu L, Huang Y, Mao Z, Zhan Z, et al. Metabolism and toxicity of emodin: Genome-wide association studies reveal hepatocyte nuclear factor 4α regulates UGT2B7 and emodin glucuronidation. Chem Res Toxicol. 2020;33(7):1798–808.
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271–80.
Li H, Yan B, Gao R, Ren J, Yang J. Effectiveness of corticosteroids to treat severe COVID-19: A systematic review and meta-analysis of prospective studies. Int Immunopharmacol. 2021;100:108121.
Xiao L, Sakagami H, Miwa N. ACE2: The key molecule for understanding the pathophysiology of severe and critical conditions of COVID-19: Demon or angel? Viruses. 2020;12(5):491.
Zhu Z, Lian X, Su X, Wu W, Marraro GA, Zeng Y. From SARS and MERS to COVID-19: A brief summary and comparison of severe acute respiratory infections caused by three highly pathogenic human coronaviruses. Respir Res. 2020;21(1):224.
Li G, Fan Y, Lai Y, Han T, Li Z, Zhou P, et al. Coronavirus infections and immune responses. J Med Virol. 2020;92(4):424–32.
Groß S, Jahn C, Cushman S, Bär C, Thum T. SARS-CoV-2 receptor ACE2-dependent implications on the cardiovascular system: From basic science to clinical implications. J Mol Cell Cardiol. 2020;144:47–53.
Borba MGS, Val FFA, Sampaio VS, Alexandre MAA, Melo GC, Brito M, et al. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: A randomized clinical trial. JAMA Netw Open. 2020;3(423):e208857.
Das S, Bhowmick S, Tiwari S, Sen S. An updated systematic review of the therapeutic role of hydroxychloroquine in coronavirus disease-19 (COVID-19). Clin Drug Investig. 2020;40(7):591–601.
Singh AK, Singh A, Singh R, Misra A. “Hydroxychloroquine in patients with COVID-19: A Systematic Review and meta-analysis.” Diabetes and Metabolic Syndrome: Clinical Research and Reviews. 2020;14(4):589–96.
Singh AK, Singh A, Shaikh A, Singh R, Misra A. Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries. Diabetes and Metabolic Syndrome: Clinical Research and Reviews. 2020;14(3):241–6.
Beyerstedt S, Casaro EB, Rangel ÉB. COVID-19: Angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection. European Journal of Clinical Microbiology and Infectious Diseases. 2021;40(5):905–19.
Ferrario CM, Jessup J, Chappell MC, Averill DB, Brosnihan KB, Tallant EA, et al. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation. 2005;111(20):2605–10.
Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. The Lancet. 2020;395(10223):507–13.
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061–9.
Downloads
Additional Files
Published
Issue
Section
License
- The authors own the copyright of published articles. Nevertheless, Jurnal Respirologi Indonesia has the first-to-publish license for the publication material.
- Jurnal Respirologi Indonesia has the right to archive, change the format and republish published articles by presenting the authors’ names.
- Articles are published electronically for open access and online for educational, research, and archiving purposes. Jurnal Respirologi Indonesia is not responsible for any copyright issues that might emerge from using any article except for the previous three purposes.