Archive \ Volume.13 2022 Issue 4

Antiviral and Anti-SARS-CoV-2 Activity of Natural Chlorogenic Acid and Its Synthetic Derivatives


Since the dawn of time, several viral epidemics have swept the globe, among them the current COVID-19 outbreak. The ongoing emergence and propagation of novel viral illnesses have compelled researchers to seek new therapeutic approaches that can get beyond the drawbacks of antivirals that are available right now. Medicinal plants have historically offered treatments for a range of illnesses. These bioactive compounds serve as the foundation for many "modern" pharmaceuticals. One of the essential polyphenols in various medicinal plants is Chlorogenic acid (CA), an ester of caffeic and quinic acid. Extensive research has revealed that CA possesses anti-inflammatory, anticarcinogenic, and antioxidant properties. This review aims to briefly summarise CA and its derivative's antiviral properties on various human viral diseases and their ability to fight the current COVID-19 disease. This review summarises CA antiviral action on the following viruses: influenza A virus (H1N1/H3N2/H7N9), hepatitis C virus (HCV) and hepatitis B virus (HBV), human immunodeficiency virus (HIV), infectious bronchitis virus (IBV), porcine reproductive and respiratory syndrome virus (PRRSV), herpes simplex virus (HSV)-1, enterovirus 71 (Ent 71), adenoviruses (AdenV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review will open the way for developing and designing potentially effective and broad-spectrum CA-based antiviral medicines.

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How to cite:
Aljehany BM. Antiviral and Anti-SARS-CoV-2 Activity of Natural Chlorogenic Acid and Its Synthetic Derivatives. Arch Pharm Pract. 2022;13(4):74-81.
Aljehany, B. M. (2022). Antiviral and Anti-SARS-CoV-2 Activity of Natural Chlorogenic Acid and Its Synthetic Derivatives. Archives of Pharmacy Practice, 13(4), 74-81.

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1.        Clifford MN. Chlorogenic acids and other cinnamates - Nature, occurrence, dietary burden, absorption and metabolism. J Sci Food Agric. 2000;80(7):1033-43.

2.        Kumar R, Sharma A, Iqbal MS, Srivastava JK.  Therapeutic promises of chlorogenic acid with special emphasis on its anti-obesity property. Curr Molecular Pharmacol. 2020;13(1):7-16.

3.        Renouf M, Guy PA, Marmet C, Fraering AL, Longet K, Moulin J, et al. Measurement of caffeic and ferulic acid equivalents in plasma after coffee consumption: Small intestine and colon are key sites for coffee metabolism. Mol Nutr Food Res. 2010;54(6):760-6.

4.        Perrone D, Farah A, Donangelo CM, de Paulis T, Martin PR. Comprehensive analysis of major and minor chlorogenic acids and lactones in economically relevant Brazilian coffee cultivars. Food Chem. 2008;106(2):859-67.

5.        Pedram S, Per BJ, Christine BC, Fredrik BM, Kjeld H, Søren G. Efficacy of arabica versus robusta coffee in improving weight, insulin resistance, and liver steatosis in a rat model of type-2 diabetes. Nutrient. 2019;11(9):2074.

6.        Kwon SH, Lee HK, Kim JA, Hong SI, Kim HC, Jo TH, et al. Neuroprotective effects of chlorogenic acid on scopolamine-induced amnesia via anti-acetylcholinesterase and anti-oxidative activities in mice. Eur J Pharmacol. 2010;649(1-3):210-7.

7.        Wang L, Pan X, Jiang L, Chu Y, Gao S, Jiang X, et al. The Biological Activity Mechanism of Chlorogenic Acid and Its Applications in Food Industry: A Review. Front Nutr. 2022;9:943911.

8.        Luan L, Wang G, Lin R. HPLC and chemometrics for the quality consistency evaluation of shuanghuanglian injection. J Chromatogr Sci. 2014;52(7):707-12.

9.        Wu S, Jin Y, Liu Q, Liu QA, Wu J, Bi YA, et al. On-line quantitative monitoring of liquid-liquid extraction of Lonicera japonica and Artemisia annua using near-infrared spectroscopy and chemometrics. Pharmacogn Mag. 2015;11(43):643-50.

10.      Deniz B, Zulfiye G, Julie AM, Betul C, Nilufer C, Mine SG. Pharmacologic overview of chlorogenic acid and its metabolites in chronic pain and inflammation. Curr Neuropharmacol. 2020;18(3):216-28.

11.      Dos Santos MD, Almeida MC, Lopes NP, De Souza GEP. Evaluation of the anti-inflammatory, analgesic and antipyretic activities of the natural polyphenol chlorogenic acid. Biol Pharm Bull. 2006;29(11):2236-40.

12.      Johnston KL, Clifford MN, Morgan LM. Coffee acutely modifies gastrointestinal hormone secretion and glucose tolerance in humans: Glycemic effects of chlorogenic acid and caffeine. Am J Clin Nutr. 2003;78(4):728-33.

13.      Thom E. The effect of chlorogenic acid enriched coffee on glucose absorption in healthy volunteers and its effect on body mass when used long-term in overweight and obese people. J Int Med Res. 2007;35(6):900-8.

14.      Lapchak PA. The phenylpropanoid micronutrient chlorogenic acid improves clinical rating scores in rabbits following multiple infarct ischemic strokes: Synergism with tissue plasminogen activator. Exp Neurol. 2007;205(2):407-13.

15.      Suzuki A, Kagawa D, Ochiai R, Tokimitsu I, Saito I. Green coffee bean extract and its metabolites have a hypotensive effect in spontaneously hypertensive rats. Hypertens Res. 2002;25(1):99-107.

16.      Tamura H, Akioka T, Ueno K, Chujyo T, Okazaki K, King PJ, et al. Anti-human immunodeficiency virus activity of 3,4,5-tricaffeoylquinic acid in cultured cells of lettuce leaves. Mol Nutr Food Res. 2006;50(4-5):396-400. 

17.      Karar M, Matei MF, Jaiswal R, Illenberger S, Kuhnert N. Neuraminidase inhibition of dietary chlorogenic acids and derivatives-potential antivirals from dietary sources. Food Funct. 2016;7(4):2052-9.

18.      Chiang LC, Chiang W, Chang MY, Ng LT, Lin CC. Antiviral activity of Plantago major extracts and related compounds in vitro. Antiviral Res. 2002;55(1):53-62.

19.      Khan MTH, Ather A, Thompson KD, Gambari R. Extracts and molecules from medicinal plants against herpes simplex viruses. Antiviral Res. 2005;67(2):107-19.

20.      Wang GF, Shi LP, Ren YD, Liu QF, Liu HF, Zhang RJ, et al. Anti-hepatitis B virus activity of chlorogenic acid, quinic acid and caffeic acid in vivo and in vitro. Antiviral Res. 2009;83(2):186-90.

21.      Liu Z, Zhao J, Li W, Shen L, Huang S, Tang J, et al. Computational screen and experimental validation of anti-influenza effects of quercetin and chlorogenic acid from traditional Chinese medicine. Sci Rep. 2016;6(1):1-9.

22.      Luo HJ, Wang JZ, Chen JF, Zou K. Docking study on chlorogenic acid as a potential H5N1 influenza A virus neuraminidase inhibitor. Med Chem Res. 2011;20(5):554-7.

23.      Liu Z, Zhao J, Li W, Wang X, Xu J, Xie J, et al. Molecular docking of potential inhibitors for influenza H7N9. Comput Math Methods Med. 2015;2015:480764. doi:10.1155/2015/480764

24.      Li L, Chang S, Xiang J, Li Q, Liang H, Tang Y, et al. Screen anti-influenza lead compounds that target the PAc subunit of H5N1 viral RNA polymerase. PLoS One. 2012;7(8). doi:10.1371/journal.pone.0035234

25.      Yu Y, Zhu C, Wang S, Song W, Yang Y, Shi J. Homosecoiridoid alkaloids with amino acid units from the flower buds of lonicera japonica. J Nat Prod. 2013;76(12):2226-33.

26.      Utsunomiya H, Ichinose M, Ikeda K, Uozaki M, Morishita J, Kuwahara T, et al. Inhibition by caffeic acid of the influenza a virus multiplication in vitro. Int J Mol Med. 2014;34(4):1020-4.

27.      Wang HP, Liu Y, Chen C, Xiao H Bin. Screening specific biomarkers of herbs using a metabolomics approach: a case study of panax ginseng. Sci Rep. 2017;7(1):4609.

28.      Satheeshkumar N, Nisha N, Sonali N, Nirmal J, Jain GK, Spandana V. Analytical profiling of bioactive constituents from herbal products, using metabolomics - A review. Natural Product Communications. 2012;7(8):1111-5.

29.      Tajik N, Tajik M, Mack I, Enck P. The potential effects of chlorogenic acid, the main phenolic components in coffee, on health: a comprehensive review of the literature. Eur J Nutr. 2017;56(7):2215-44.

30.      McAuley JL, Gilbertson BP, Trifkovic S, Brown LE, McKimm-Breschkin JL. Influenza virus neuraminidase structure and functions. Front Microbiol. 2019;10(JAN):39.

31.      Parra-Rojas C, Nguyen VK, Hernandez-Mejia G, Hernandez-Vargas EA. Neuraminidase Inhibitors in influenza treatment and prevention–is it time to call it a day? Viruses. 2018;10(9):454.

32.      Farrukee R, Hurt AC. Antiviral Drugs for the treatment and prevention of influenza. Curr Treat Options Infect Dis 2017 93. 2017;9(3):318-32.

33.      Ren J, Huang J, Yang B, Lin S, Li J, Liao H, et al. Docking and molecular dynamics: simulation of the inhibition of H5N1 influenza virus (Anhui 2005) neuraminidase (NA) by chlorogenic acid (CHA). Int J Clin Exp Med. 2019;12(8):9815-23.

34.      Ding Y, Cao Z, Cao L, DIng G, Wang Z, Xiao W. Antiviral activity of chlorogenic acid against influenza A (H1N1/H3N2) virus and its inhibition of neuraminidase. Sci Rep. 2017;7:45723.

35.      Kaihatsu K, Kawakami C, Kato N. Potential anti-influenza virus agents based on coffee ingredients and natural flavonols. Nat Prod Chem Res. 2014;2(2):1000129.

36.      Kuwata K, Urushisaki T, Takemura T, Tazawa S, Fukuoka M, Hosokawa-Muto J, et al. Caffeoylquinic acids are major constituents with potent anti-influenza effects in brazilian green propolis water extract. Evidence-based Complement Altern Med. 2011;2011:1-7.

37.      Sidorkiewicz M. Hepatitis C Virus Uses Host Lipids to Its Own Advantage. Metabolites. 2021;11(5):273. 

38.      El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142(6):1264-73.

39.      Hoshida Y, Fuchs BC, Bardeesy N, Baumert TF, Chung RT. Pathogenesis and prevention of hepatitis C virus-induced hepatocellular carcinoma. J Hepatol. 2014;61(10):S79-90.

40.      Braillon A. Interferon-free treatments against HCV are far from free. Lancet (London, England). 2015;386(9996):856.

41.      Spengler U. Direct antiviral agents (DAAs) - A new age in the treatment of hepatitis C virus infection. Pharmacol Ther. 2018;183:118-26. 

42.      Shirasago Y, Inamori Y, Suzuki T, Tanida I, Suzuki T, Sugiyama K, et al. Inhibition mechanisms of hepatitis C virus infection by caffeic acid and tannic acid. Biol Pharm Bull. 2019;42(5):770-7.

43.      Cook JKA, Jackwood M, Jones RC. The long view: 40 years of infectious bronchitis research. Avian Pathol. 2012;41(3):239-50.

44.      Ignjatović J, Sapats S. Avian infectious bronchitis virus. Rev Sci Tech. 2000;19(2):493-508. 

45.      Lin SY, Chen HW. Infectious Bronchitis Virus Variants: Molecular Analysis and Pathogenicity Investigation. Int J Mol Sci. 2017;18(10):2030. 

46.      Bande F, Arshad SS, Omar AR, Hair-Bejo M, Mahmuda A, Nair V. Global distributions and strain diversity of avian infectious bronchitis virus: a review. Anim Heal Res Rev. 2017;18(1):70-83.

47.      King AM, Lefkowitz E, Adams MJ, Carstens EB, editors. Virus taxonomy: ninth report of the International Committee on Taxonomy of Viruses. Elsevier; 2011.

48.      Fan WQ, Wang HN, Zhang Y, Guan Z Bin, Wang T, Xu CW, et al. Comparative dynamic distribution of avian infectious bronchitis virus M41, H120, and SAIBK strains by quantitative real-time RT-PCR in SPF chickens. Biosci Biotechnol Biochem. 2012;76(12):2255-60.

49.      Yu L, Jiang Y, Low S, Wang Z, Nam SJ, Liu W, et al. Characterization of three infectious bronchitis virus isolates from China associated with proventriculus in vaccinated chickens. Avian Dis. 2001;45(2):416-24.

50.      Benyeda Z, Mató T, Süveges T, Szabó É, Kardi V, Abonyi-Tóth Z, et al. Comparison of the pathogenicity of QX-like, M41 and 793/B infectious bronchitis strains from different pathological conditions. Avian Pathol. 2009;38(6):449-56.

51.      Cavanagh D. Coronavirus avian infectious bronchitis virus. Vet Res. 2007;38(2):281-97.

52.      Abaidullah M, Peng S, Song X, Zou Y, Li L, Jia R, et al. Chlorogenic acid is a positive regulator of MDA5, TLR7 and NF-κB signaling pathways mediated antiviral responses against Gammacoronavirus infection. Int Immunopharmacol. 2021;96:107671. 

53.      Salehi B, Anil Kumar NV, Şener B, Sharifi-Rad M, Kılıç M, Mahady GB, et al. Medicinal plants used in the treatment of human immunodeficiency virus. Int J Molecul Sci. 2018;19(5):1459.

54.      Patel P, Zulfiqar H. Reverse transcriptase inhibitors. Front HIV Res. 2022;44-61.

55.      Heyman HM, Senejoux F, Seibert I, Klimkait T, Maharaj VJ, Meyer JJ. Identification of anti-HIV active dicaffeoylquinic- and tricaffeoylquinic acids in Helichrysum populifolium by NMR-based metabolomic guided fractionation. Fitoterapia. 2015;103:155-64. 

56.      Esposito F, Sanna C, Del Vecchio C, Cannas V, Venditti A, Corona A, et al. Hypericum hircinum L. components as new single-molecule inhibitors of both HIV-1 reverse transcriptase-associated DNA polymerase and ribonuclease H activities. Pathog Dis. 2013;68(3):116-24.

57.      Cihlar T, Ray AS. Nucleoside and nucleotide HIV reverse transcriptase inhibitors: 25 years after zidovudine. Antiviral Res. 2010;85(1):39-58.

58.      de Béthune MP. Non-nucleoside reverse transcriptase inhibitors (NNRTIs), their discovery, development, and use in the treatment of HIV-1 infection: a review of the last 20 years (1989-2009). Antiviral Res. 2010;85(1):75-90. 

59.      De Clercq E. Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. Int J Antimicrob Agents. 2009;33(4):307-20.

60.      Castro CB, Luz LR, Guedes JAC, Porto DD, Silva MFS, Silva GS, et al. Metabolomics-based discovery of biomarkers with cytotoxic potential in extracts of Myracrodruon urundeuva. J Braz Chem Soc. 2020;31(4):775-87.

61.      Emamzadeh Yazdi S, Heyman HM, Prinsloo G, Klimkait T, Meyer JJM. Identification of Anti-HIV Biomarkers of Helichrysum Species by NMR-Based Metabolomic Analysis. Front Pharmacol. 2022;13:904231.

62.      Li J, Dou L, Chen S, Zhou H, Mou F. Neochlorogenic acid: an anti-HIV active compound identified by screening of Cortex Mori [Morus Alba L. (Moraceae)]. Pharm Biol. 2021;59(1):1517-27.

63.      Huerta-Reyes M, Sánchez-Vargas LO, Villanueva-Amador GS, Gaitán-Cepeda LA. Anti-hiv and anti-candidal effects of methanolic extract from heteropterys brachiata. Int J Environ Res Public Health. 2021;18(14):7270.

64.      Tamayose CI, Torres PB, Roque N, Ferreira MJP. HIV-1 reverse transcriptase inhibitory activity of flavones and chlorogenic acid derivatives from Moquiniastrum floribundum (Asteraceae). South African J Bot. 2019;123:142-6.

65.      Ramdas P, Sahu AK, Mishra T, Bhardwaj V, Chande A. From Entry to Egress: Strategic Exploitation of the Cellular Processes by HIV-1. Front Microbiol. 2020;11:3021.

66.      Serina JC, Castilho PC, Fernandes MX. Caffeoylquinic acids as inhibitors for HIV-I protease and HIV-I Integrase. A Molecular docking study. SDRP J Comput Chem Mol Model. 2017;1(2):1-4.

67.      Kwon HC, Jung CM, Shin CG, Lee JK, Choi SU, Kim SY, et al. A new caffeoyl quinic acid from aster scaber and its inhibitory activity against human immunodeficiency virus-1 (HIV-1) integrase. Chem Pharm Bull (Tokyo). 2000;48(11):1796-8. 

68.      Mcdougall B, King PJ, Wu BW, Hostomsky Z, Reinecke MG, Robinson WE. Dicaffeoylquinic and dicaffeoyltartaric acids are selective inhibitors of human immunodeficiency virus type 1 integrase. Antimicrob Agents Chemother. 1998;42(1):140-6.

69.      Cheng J, Sun N, Zhao X, Niu L, Song M, Sun Y, et al. In vitro screening for compounds derived from traditional chinese medicines with antiviral activities against porcine reproductive and respiratory syndrome virus. J Microbiol Biotechnol. 2013;23(8):1076-83.

70.      Solomon T, Lewthwaite P, Perera D, Cardosa MJ, McMinn P, Ooi MH. Virology, epidemiology, pathogenesis, and control of enterovirus 71. Lancet Infect Dis. 2010;10(11):778-90.

71.      Wong SSY, Yip CCY, Lau SKP, Yuen KY. Human enterovirus 71 and hand, foot and mouth disease. Epidemiol Infect. 2010;138(8):1071-89.

72.      Han Y, Wang L, Cui J, Song Y, Luo Z, Chen J, et al. SIRT1 inhibits EV71 genome replication and RNA translation by interfering with the viral polymerase and 5'UTR RNA. J Cell Sci. 2016;129(24):4534-47.

73.      Hsu CH, Lu CY, Shao PL, Lee PI, Kao CL, Chung MY, et al. Epidemiologic and clinical features of non-polio enteroviral infections in northern Taiwan in 2008. J Microbiol Immunol Infect. 2011;44(4):265-73.

74.      Irani DN. Aseptic meningitis and viral myelitis. Neurol Clin. 2008;26(3):635-55.

75.      Li X, Liu Y, Hou X, Peng H, Zhang L, Jiang Q, et al. Chlorogenic acid inhibits the replication and viability of enterovirus 71 in vitro. PLoS One. 2013;8(9):e76007.

76.      Lynch JP, Kajon AE. Adenovirus: epidemiology, global spread of novel serotypes, and advances in treatment and prevention. Semin Respir Crit Care Med. 2016;37(4):586-602.

77.      Musarra-Pizzo M, Pennisi R, Ben-Amor I, Mandalari G, Sciortino MT. Antiviral activity exerted by natural products against human viruses. Viruses. 2021;13(5):828.

78.      Deng N, Wang J. Interference of chlorogenic acid on tlr2 signal pathway in hsv-1 infected microglia. Her Med. 2018;37(10):1170-3.

79.      Hasöksüz M, Kiliç S, Saraç F. Coronaviruses and sars-cov-2. Turkish J Med Sci. 2020;50(SI-1):549-56.

80.      Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020;75(7):1730-41. 

81.      Tong T, Wu YQ, Ni WJ, Shen AZ, Liu S. The potential insights of Traditional Chinese Medicine on treatment of COVID-19. Chin Med. 2020;15:51.

82.      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.

83.      Kzhyshkowska J. Stabilizing the immune system by chlorogenic acid. J Leukoc Biol. 2022;112(1):7-8.

84.      Li QR, Tan SR, Yang L, He W, Chen L, Shen FX, et al. Mechanism of chlorogenic acid in alveolar macrophage polarization in Klebsiella pneumoniae-induced pneumonia. J Leukoc Biol. 2022;112(1):9-21.

85.      Jain S, Saha P, Panda SR, Sharma P, Naidu VGM. Chlorogenic Acid Alleviates LPS/POLY:IC Induced Oxidative Stress, Cytokine Storm and Platelet Aggregation in an ALI Model. 2022:A2008.

86.      El Gizawy HA, Boshra SA, Mostafa A, Mahmoud SH, Ismail MI, Alsfouk AA, et al. Pimenta dioica (L.) merr. bioactive constituents exert anti-sars-cov-2 and anti-inflammatory activities: Molecular docking and dynamics, in vitro, and in vivo studies. Molecules. 2021;26(19):5844.

87.      Perdomo R, Yerima F, Mahoney O, Cornejal N, Alsaidi S, Coron S, et al. Antioxidant, antibacterial, and anti-SARS-CoV Activity of Commercial Products of Xylopia (Xylopia aethiopica). J Med Act Plants. 2021;10(1):11-23.

88.      Wang Z, Xu C, Liu B, Qiao N. Repurposing the natural compound for antiviral during an epidemic. ChemRxiv. 2020;Preprint. doi:10.26434/chemr

89.      Wang WX, Zhang YR, Luo SY, Zhang Y Sen, Zhang Y, Tang C. Chlorogenic acid, a natural product as potential inhibitor of COVID-19: virtual screening experiment based on network pharmacology and molecular docking. Nat Prod Res. 2022;36(10):2580-4.

90.      Wang LN, Wang W, Hattori M, Daneshtalab M, Ma CM. Synthesis, anti-HCV, antioxidant and reduction of intracellular reactive oxygen species generation of a chlorogenic acid analogue with an amide bond replacing the ester bond. Molecules. 2016;21(6):737.

91.      Sinisi V, Stevaert A, Berti F, Forzato C, Benedetti F, Navarini L, et al. Chlorogenic Compounds from Coffee Beans Exert activity against respiratory viruses. Planta Med. 2017;83(7):615-23.

92.      Assefa ST, Yang EY, Chae SY, Song M, Lee J, Cho MC, et al. Alpha glucosidase inhibitory activities of plants with focus on common vegetables. Plants. 2020;9(1):2.

93.      Lambert GS, Upadhyay C. HIV-1 Envelope Glycosylation and the Signal Peptide. Vaccines (Basel). 2021;9(2):176. 

94.      Hattori M, Ma CM, Wei Y, Salah R, Dine E, Sato N. α-glucosidase inhibitors as host-directed antiviral agents with potential for the treatment of COVID-19. Biochem Soc Trans. 2020;48:1287-95.



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