Antiviral Activity of Cinchona officinalis, a Homeopathic Medicine, against COVID-19

Abstract

Background Coronavirus disease 2019 (COVID-19) is a potentially fatal disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several studies have shown that hydroxychloroquine (HCQ) significantly inhibits SARS-CoV-2 infections in vitro.

Objective Since the phytoconstituents of Cinchona officinalis (CO) are similar to those of HCQ, the objective of this study was to test the antiviral potential of different homeopathic formulations of CO.

Methods An analysis of the molecular composition of CO was carried out using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, followed by a detailed docking study. The constituents of CO were docked against various targets of SARS-CoV-2, and the binding potential of the phytoconstituents was compared and quantified. The ligand with the lowest Glide docking score is considered to have the best binding affinity. The cytotoxicity of several homeopathic formulations, including CO mother tincture (CO-MT), was also checked on VeroE6 cells. A known antiviral, remdesivir, was used as a positive control for the in vitro assays to evaluate the effects of CO-MT against SARS-CoV-2-infected VeroE6 cells.

Results Molecular docking studies showed that constituents of CO exhibited binding potential to various targets of SARS-CoV-2, including Mpro, PLpro, RdRp, nucleocapsid protein, ACE2 (in host) and spike protein. Quinoline, one of the constituents of CO, can potentially bind the spike protein of SARS-CoV-2. Quinic acid showed better binding capabilities with Mpro, PLpro RdRp, nucleocapsid protein and ACE2 (allosteric site) than other constituents. Quinidine exhibited better binding to ACE2. Compared to HCQ, other phytoconstituents of CO had the equivalent potential to bind the RNA-dependent RNA polymerase, nucleocapsid protein, Mpro, PLpro and spike protein of SARS-CoV-2. In vitro assays showed that homeopathic CO-MT was not cytotoxic and that CO-MT and remdesivir respectively caused 89% and 99% inhibition of SARS-CoV-2 infection in VeroE6 cells.

Conclusion Based on this in silico and in vitro evidence, we propose CO-MT as a promising antiviral medicine candidate for treating COVID-19. In vivo investigation is required to clarify the therapeutic potential of CO-MT in COVID-19.

Keywords

Homeopathy - Cinchona officinalis - COVID-19 - antiviral - toxicity - docking

Publication History

Received: 06 February 2023

Accepted: 20 April 2023

Article published online:
06 September 2023

• References

• 1 Zhu L, Xu X, Ma K. et al. Successful recovery of COVID-19 pneumonia in a renal transplant recipient with long-term immunosuppression. Am J Transplant 2020; 20: 1859-1863
• 2 Zhang H, Chen Y, Yuan Q. et al. Identification of kidney transplant recipients with coronavirus disease 2019. Eur Urol 2020; 77: 742-747
• 3 Zhu N, Zhang D, Wang W. et al; China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020; 382: 727-733
• 4 Liu K, Fang YY, Deng Y. et al. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J (Engl) 2020; 133: 1025-1031
• 5 Wang D, Hu B, Hu C. et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020; 323: 1061-1069
• 6 Patel VK, Shirbhate E, Patel P, Veerasamy R, Sharma PC, Rajak H. Corticosteroids for treatment of COVID-19: effect, evidence, expectation and extent. Beni Suef Univ J Basic Appl Sci 2021; 10: 78
• 7 Manchanda RK, Miglani A, Gupta M. et al. Homeopathic remedies in COVID-19: prognostic factor research. Homeopathy 2021; 110: 160-167
• 8 Remya V, Kuttan G. Homeopathic remedies with antineoplastic properties have immunomodulatory effects in experimental animals. Homeopathy 2015; 104: 211-219
• 9 Holmfred E, Cornett C, Maldonado C, Rønsted N, Hansen SH. An optimised method for routine separation and quantification of major alkaloids in cortex Cinchona by HPLC coupled with UV and fluorescence detection. Phytochem Anal 2017; 28: 374-380
• 10 Rajan A, Bagai U, Chandel S. Effect of artesunate based combination therapy with homeopathic medicine china on liver and kidney of Plasmodium berghei infected mice. J Parasit Dis 2013; 37: 62-67
• 11 Narożna M, Rubiś B. Anti-SARS-CoV-2 strategies and the potential role of miRNA in the assessment of COVID-19 morbidity, recurrence, and therapy. Int J Mol Sci 2021; 22: 8663
• 12 Yao X, Ye F, Zhang M. et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis 2020; 71: 732-739
• 13 Panusa A, Multari G, Incarnato G, Gagliardi L, McCalley DV. Analysis of the Cinchona alkaloids by high-performance liquid chromatography and other separation techniques. J Pharm Biomed Anal 2007; 43: 1221-1227
• 14 Murugan NA, Kumar S, Jeyakanthan J, Srivastava V. Searching for target-specific and multi-targeting organics for Covid-19 in the Drugbank database with a double scoring approach. Sci Rep 2020; 10: 19125
• 15 Gordon DE, Jang GM, Bouhaddou M. et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 2020; 583: 459-468
• 16 Repasky MP, Shelley M, Friesner RA. Flexible ligand docking with Glide. Curr Protoc Bioinformatics 2007; Chapter 8: 12
• 17 Sunila ES, Kuttan R, Preethi KC, Kuttan G. Dynamized preparations in cell culture. Evid Based Complement Alternat Med 2009; 6: 257-263
• 18 Caldas LA, Carneiro FA, Higa LM. et al. Ultrastructural analysis of SARS-CoV-2 interactions with the host cell via high resolution scanning electron microscopy. Sci Rep 2020; 10: 16099
• 19 Runfeng L, Yunlong H, Jicheng H. et al. Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2). Pharmacol Res 2020; 156: 104761
• 20 Ogando NS, Dalebout TJ, Zevenhoven-Dobbe JC. et al. SARS-coronavirus-2 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology. J Gen Virol 2020; 101: 925-940
• 21 Gosik MS, Mendes MFX, Werneck Dos Santos LMA. et al. Medicines for the new coronavirus in the view of classical systemic homeopathy. Complement Ther Clin Pract 2021; 45: 101482