Generic placeholder image

Current Drug Therapy


ISSN (Print): 1574-8855
ISSN (Online): 2212-3903

Review Article

Natural Product-derived Phytochemicals as Potential Inhibitors of Angiotensin Converting Enzyme 2 (ACE2): Promising Drug Candidates for COVID-19

Author(s): Aparna D. Palshetkar, Aarti U. Rasal, Aruna Murugan and Namita D. Desai*

Volume 19, Issue 1, 2024

Published on: 19 May, 2023

Page: [13 - 19] Pages: 7

DOI: 10.2174/1574885518666230502103159

Price: $65


COVID-19 was deemed a global pandemic by the World Health Organization in February 2020. The prevalence of viral diseases worldwide has increased the importance of receiving immediate medical attention. There is currently no specific medication or vaccine under consideration to treat coronavirus infection. For reducing or preventing COVID-19 infections, a number of alternative therapies are anticipated, including the use of synthetic drugs, vaccines, interferon therapy etc. Due to the serious side effects of the utilized drug therapies, it is crucial to comprehend the pathogenesis of the coronavirus and explore safe and efficient treatment.

Considering the contribution of plants and herbs in the management of viruses like HIV, Herpes Simplex, MERS-CoV, and influenza, they can be further utilised for COVID-19 treatment. According to reports, SARS-CoV2 infects host cells through Angiotensin-converting enzyme 2 receptors, causing pneumonia linked to COVID-19 as well as acute myocardial injury and long-term cardiovascular damage. A cure for SARS-CoV2 may lie in understanding the receptor, its targets, and the mechanism of viral replication. This review article highlights several plants that have the potential to inhibit ACE2, including Punica granatum, Citrus aurantium, Allium sativum, Piper longum, Curcuma longa, and Coriandrum sativum as well as their extracts and phytoconstituents, such as flavonoids, alkaloids, anthraquinone glycosides, phenolic acids, and others. This review will provide opportunities for researchers to explore the possibility of developing promising dosage forms that will increase the bioavailability and in vivo effectiveness of the lead candidates.

Keywords: Coronavirus 2019, SARS-CoV, angiotensin-converting enzyme-2, medicinal plants, phytochemicals, therapeutic use.

Graphical Abstract
Pal M, Berhanu G, Desalegn C, Kandi V. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): An update. Cureus 2020; 12(3): e7423.
[] [PMID: 32337143]
Singhal T. A review of coronavirus disease-2019 (COVID-19). Indian J Pediatr 2020; 87(4): 281-6.
[] [PMID: 32166607]
Khuroo MS, Sofi AA, Khuroo M. Chloroquine and hydroxychloroquine in coronavirus disease 2019 (COVID-19). Facts, fiction and the hype: A critical appraisal. Int J Antimicrob Agents 2020; 56(3): 106101.
[] [PMID: 32687949]
Qomara WF, Primanissa DN, Amalia SH, Purwadi FV, Zakiyah N. Effectiveness of remdesivir, lopinavir/ritonavir, and favipiravir for COVID-19 treatment: A systematic review. Int J Gen Med 2021; 14: 8557-71.
[] [PMID: 34849001]
Lu H. Drug treatment options for the 2019-new coronavirus (2019-nCoV). Biosci Trends 2020; 14(1): 69-71.
[] [PMID: 31996494]
Ganjhu RK, Mudgal PP, Maity H, et al. Herbal plants and plant preparations as remedial approach for viral diseases. Virusdisease 2015; 26(4): 225-36.
[] [PMID: 26645032]
Fehr AR, Perlman S. Coronaviruses: An overview of their replication and pathogenesis. Methods Mol Biol 2015; 1282: 1-23.
[] [PMID: 25720466]
Siu YL, Teoh KT, Lo J, et al. The M, E, and N structural proteins of the severe acute respiratory syndrome coronavirus are required for efficient assembly, trafficking, and release of virus-like particles. J Virol 2008; 82(22): 11318-30.
[] [PMID: 18753196]
Tang T, Bidon M, Jaimes JA, Whittaker GR, Daniel S. Coronavirus membrane fusion mechanism offers a potential target for antiviral development. Antiviral Res 2020; 178: 104792.
[] [PMID: 32272173]
Shang J, Ye G, Shi K, et al. Structural basis of receptor recognition by SARS-CoV-2. Nature 2020; 581(7807): 221-4.
[] [PMID: 32225175]
Ni W, Yang X, Yang D, et al. Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19. Crit Care 2020; 24(1): 422.
[] [PMID: 32660650]
Bourgonje AR, Abdulle AE, Timens W, et al. Angiotensi CoV 2 and the pathophysiology of coronavirus disease 2019 (COVID 19). J Pathol 2020; 251(3): 228-48.
[] [PMID: 32418199]
Duan L, Zheng Q, Zhang H, Niu Y, Lou Y, Wang H. The SARS-CoV-2 spike glycoprotein biosynthesis, structure, function, and antigenicity: Implications for the design of spike-based vaccine immunogens. Front Immunol 2020; 11: 576622.
[] [PMID: 33117378]
Burrell LM, Johnston CI, Tikellis C, Cooper ME. ACE2, a new regulator of the renin–angiotensin system. Trends Endocrinol Metab 2004; 15(4): 166-9.
[] [PMID: 15109615]
Barbosa-Filho JM, Martins VKM, Rabelo LA, et al. Natural products inhibitors of the angiotensin converting enzyme (ACE): A review between 1980 - 2000. Rev Bras Farmacogn 2006; 16(3): 421-46.
Antonio AS, Wiedemann LSM, Veiga-Junior VF. Natural products’ role against COVID-19. RSC Advances 2020; 10(39): 23379-93.
[] [PMID: 35693131]
Guerrero L, Castillo J, Quiñones M, et al. Inhibition of angiotensin-converting enzyme activity by flavonoids: structure-activity relationship studies. PLoS One 2012; 7(11): e49493.
[] [PMID: 23185345]
Pande M, Kundu D, Srivastava R. Drugs repurposing against SARS-CoV2 and the new variant B.1.1.7 (alpha strain) targeting the spike protein: molecular docking and simulation studies. Heliyon 2021; 7(8): e07803.
[] [PMID: 34423145]
Xu J, Gao L, Liang H, Chen S. In silico screening of potential anti–COVID-19 bioactive natural constituents from food sources by molecular docking. Nutrition 2021; 82: 111049.
[] [PMID: 33290972]
Panche AN, Diwan AD, Chandra SR. Flavonoids: An overview. J Nutr Sci 2016; 5(e47): e47.
[] [PMID: 28620474]
Siegel AB, Stebbing J. Milk thistle: Early seeds of potential. Lancet Oncol 2013; 14(10): 929-30.
[] [PMID: 23993379]
Tungmunnithum D, Thongboonyou A, Pholboon A, Yangsabai A. Flavonoids and other phenolic compounds from medicinal plants for pharmaceutical and medical aspects: An overview. Medicines 2018; 5(3): 93.
[] [PMID: 30149600]
Godinho PIC, Soengas RG, Silva VLM. Therapeutic potential of glycosyl flavonoids as anti-coronaviral agents. Pharmaceuticals 2021; 14(6): 546.
[] [PMID: 34200456]
Dirks ML, Seale JT, Collins JM, McDougal OM. Review: Veratrum californicum Alkaloids. Molecules 2021; 26(19): 5934.
[] [PMID: 34641477]
Rahman Md. In silico investigation and potential therapeutic approaches of natural products for COVID-19: Computer-aided drug design perspective. Front Cell Infect Microbiol 2022; 12: 929430.
Ho T, Wu S, Chen J, Li C, Hsiang C. Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction. Antiviral Res 2007; 74(2): 92-101.
[] [PMID: 16730806]
Jamal QMS. Antiviral potential of plants against COVID-19 during outbreaks—An update. Int J Mol Sci 2022; 23(21): 13564.
[] [PMID: 36362351]
Paudel P, Shrestha S, Park SE, et al. Emodin derivatives as multi-target-directed ligands inhibiting monoamine oxidase and antagonizing vasopressin V 1A receptors. ACS Omega 2020; 5(41): 26720-31.
[] [PMID: 33110998]
Deng YF, Aluko RE, Jin Q, Zhang Y, Yuan LJ. Inhibitory activities of baicalin against renin and angiotensin-converting enzyme. Pharm Biol 2012; 50(4): 401-6.
[] [PMID: 22136493]
Nong NTP, Sutopo CCY, Hung WT, Wu PH, Hsu JL. The molecular docking and inhibition kinetics of angiotensin I-converting enzyme inhibitory peptides derived from soft-shelled turtle yolk. Appl Sci 2022; 12(23): 12340.
Khamto N, Utama K, Tateing S, et al. Discovery of natural bisbenzylisoquinoline analogs from the library of Thai traditional plants as SARS-CoV-2 3CLPro inhibitors: In silico molecular docking, molecular dynamics, and in vitro enzymatic activity. J Chem Inf Model 2023.
Yang Y, Islam MS, Wang J, Li Y, Chen X. Traditional Chinese medicine in the treatment of patients infected with 2019-new coronavirus (SARS-CoV-2): A review and perspective. Int J Biol Sci 2020; 16(10): 1708-17.
[] [PMID: 32226288]
Liskova A, Samec M, Koklesova L, et al. Flavonoids against the SARS-CoV-2 induced inflammatory storm. Biomed Pharmacother 2021; 138: 111430.
[] [PMID: 33662680]
Vimalanathan S, Ignacimuthu S, Hudson JB. Medicinal plants of Tamil Nadu (Southern India) are a rich source of antiviral activities. Pharm Biol 2009; 47(5): 422-9.
Mukherjee PK, Maity N, Nema NK, Sarkar BK. Standardized Clitoria ternatea leaf extract as hyaluronidase, elastase and matrix-metalloproteinase-1 inhibitor. Indian J Pharmacol 2012; 44(5): 584-7.
[] [PMID: 23112418]
Vellingiri B, Jayaramayya K, Iyer M, et al. COVID-19: A promising cure for the global panic. Sci Total Environ 2020; 725: 138277.
[] [PMID: 32278175]
Jough SS, Saini RK, Parveen A. A Comprehensive Study on Anti-hypertensive properties of Punica granatum (Pomegranate), Cynara scolymus (Artichoke), Coscinium fenestratum (Yellow vine) in Phytopharmacological, Molecular Biology Researches. Asian J Res Pharm Sci 2021; 11(2): 126-32.
Hussain F, Jahan N, Rahman K, Sultana B, Jamil S. Identification of hypotensive biofunctional compounds of Coriandrum sativum and evaluation of their angiotensin-converting enzyme (ACE) inhibition potential. Oxid Med Cell Longev 2018; 2018: 1-11.
[] [PMID: 30581531]
Khan MY, Kumar V. Mechanism & inhibition kinetics of bioassay-guided fractions of Indian medicinal plants and foods as ACE inhibitors. J Tradit Complement Med 2019; 9(1): 73-84.
[] [PMID: 30671369]
He L, Qi Y, Rong X, et al. The Ayurvedic Medicine Salacia oblonga Attenuates Diabetic Renal Fibrosis in Rats: Suppression of Angiotensin II/AT1 Signaling. Evid Based Complement Alternat Med 2011; 2011: nep095.
[] [PMID: 19706694]
AYUSH Ministry of Health Corona Advisory – D.O. No. S. 16030/18/2019 – NAM.. 2020.
Joshi T, Joshi T, Sharma P, et al. In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking. Eur Rev Med Pharmacol Sci 2020; 24(8): 4529-36.
[] [PMID: 32373991]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy