Login Register Cart 0
Generic placeholder image

Coronaviruses

Editor-in-Chief

ISSN (Print): 2666-7967
ISSN (Online): 2666-7975

Back
Journal Home About Journal Editorial Board Current Issue Volumes/Issues
Subscribe
Perspective

Cordycepin and its Nucleoside Analogs for the Treatment of Systemic COVID-19 Infection

Author(s): P. Chellapandi* and S. Saranya

Volume 3, Issue 1, 2022

Published on: 10 September, 2021

Article ID: e221221196360 Pages: 6

DOI: 10.2174/2666796702666210910111551

Price: $65

Abstract

Coronavirus disease (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a new coronavirus isolated from Wuhan, China. It is a global health emergency, and there is no effective antiviral therapeutics available to date. Continuous structural genomic insights of SARS-CoV-2 proteins provide a warranty for the development of rational- based antivirals. Nevertheless, a structure-based drug candidate with multiple therapeutic actions would be a practical choice of medication in the treatment of severe COVID-19 patients. Cordycepin from medicinal fungi (Cordyceps spp.) and its nucleoside analogs targeting viral RNAdependent RNA polymerase and human RNase L have potent antiviral activity against various human viruses with additional immunomodulatory and anti-inflammatory effects. Anti-inflammation treatment is of pivotal importance and should be timely tailored to the individual patient along with antivirals. Our perspective on the combined antiviral and anti-inflammatory effects of cordycepin and its analogs suggests them as new therapeutics in the treatment of systemic COVID-19 infection.

Keywords: COVID-19, SARS-CoV-2, cordycepin, medicinal fungi, RNA-dependent RNA polymerase, anti-inflammation.

Graphical Abstract

[1]
Yadav PD, Potdar VA, Choudhary ML, et al. Full-genome sequences of the first two SARS-CoV-2 viruses from India. Indian J Med Res 2020; 151(2 & 3): 200-9.
[http://dx.doi.org/10.4103/ijmr.ijmr_663_20] [PMID: 32242873]
[2]
Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature 2020; 579(7798): 265-9.
[http://dx.doi.org/10.1038/s41586-020-2008-3] [PMID: 32015508]
[3]
Li G, De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov 2020; 19(3): 149-50.
[http://dx.doi.org/10.1038/d41573-020-00016-0] [PMID: 32127666]
[4]
Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020; 30(3): 269-71.
[http://dx.doi.org/10.1038/s41422-020-0282-0] [PMID: 32020029]
[5]
Zhang W, Zhao Y, Zhang F, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (covid-19): the perspectives of clinical immunologists from china. Clin Immunol 2020; 214: 108393.
[http://dx.doi.org/10.1016/j.clim.2020.108393] [PMID: 32222466]
[6]
Wang HB, Duan MX, Xu M, et al. Cordycepin ameliorates cardiac hypertrophy via activating the AMPKα pathway. J Cell Mol Med 2019; 23(8): 5715-27.
[http://dx.doi.org/10.1111/jcmm.14485] [PMID: 31225721]
[7]
Kodama EN, McCaffrey RP, Yusa K, Mitsuya H. Antileukemic activity and mechanism of action of cordycepin against terminal deoxynucleotidyl transferase-positive (TdT+) leukemic cells. Biochem Pharmacol 2000; 59(3): 273-81.
[http://dx.doi.org/10.1016/S0006-2952(99)00325-1] [PMID: 10609556]
[8]
Lee JB, Adrower C, Qin C, Fischer PM, de Moor CH, Gershkovich P. Development of cordycepin formulations for preclinical and clinical studies. AAPS PharmSciTech 2017; 18(8): 3219-26.
[http://dx.doi.org/10.1208/s12249-017-0795-0] [PMID: 28560504]
[9]
Qin P, Li X, Yang H, Wang ZY, Lu D. Therapeutic potential and biological applications of cordycepin and metabolic mechanisms in cordycepin-producing fungi. Molecules 2019; 24(12): 2231.
[http://dx.doi.org/10.3390/molecules24122231] [PMID: 31207985]
[10]
Xu JC, Zhou XP, Wang XA, et al. Cordycepin induces apoptosis and G2/M phase arrest through the ERK pathways in esophageal cancer cells. J Cancer 2019; 10(11): 2415-24.
[http://dx.doi.org/10.7150/jca.32071] [PMID: 31258746]
[11]
Rose KM, Bell LE, Jacob ST. Specific inhibition of chromatin-associated poly(A) synthesis in vitro by cordycepin 5′-triphosphate. Nature 1977; 267(5607): 178-80.
[http://dx.doi.org/10.1038/267178a0] [PMID: 16073440]
[12]
Wong YY, Moon A, Duffin R, et al. Cordycepin inhibits protein synthesis and cell adhesion through effects on signal transduction. J Biol Chem 2010; 285(4): 2610-21.
[http://dx.doi.org/10.1074/jbc.M109.071159] [PMID: 19940154]
[13]
Ryu E, Son M, Lee M, et al. Cordycepin is a novel chemical suppressor of Epstein-Barr virus replication. Oncoscience 2014; 1(12): 866-81.
[http://dx.doi.org/10.18632/oncoscience.110] [PMID: 25621301]
[14]
Tan L, Song X, Ren Y, et al. Anti-inflammatory effects of cordycepin: A review. Phytother Res 2020; 35: 1284-97.
[http://dx.doi.org/10.1002/ptr.6890] [PMID: 33090621]
[15]
Cheek MA, Sharaf ML, Dobrikov MI, Shaw BR. Inhibition of hepatitis C viral RNA-dependent RNA polymerase by α-P-boranophosphate nucleotides: exploring a potential strategy for mechanism-based HCV drug design. Antiviral Res 2013; 98(2): 144-52.
[http://dx.doi.org/10.1016/j.antiviral.2013.02.014] [PMID: 23466667]
[16]
Pizarro JM, Pizarro JL, Fernández J, Sandino AM, Spencer E. Effect of nucleotide analogues on rotavirus transcription and replication. Virology 1991; 184(2): 768-72.
[http://dx.doi.org/10.1016/0042-6822(91)90449-L] [PMID: 1653498]
[17]
Sáez-Álvarez Y, Arias A, Del Águila C, Agudo R. Development of a fluorescence-based method for the rapid determination of Zika virus polymerase activity and the screening of antiviral drugs. Sci Rep 2019; 9(1): 5397.
[http://dx.doi.org/10.1038/s41598-019-41998-1] [PMID: 30932009]
[18]
Eyer L, Fojtíková M, Nencka R, Rudolf I, Hubálek Z, Ruzek D. Viral RNA-dependent RNA polymerase inhibitor 7-Deaza-2′-C-methyladenosine prevents death in a mouse model of West Nile virus infection. Antimicrob Agents Chemother 2019; 63(3): e02093-18.
[http://dx.doi.org/10.1128/AAC.02093-18] [PMID: 30642926]
[19]
Elfiky AA. Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Life Sci 2020; 248: 117477.
[http://dx.doi.org/10.1016/j.lfs.2020.117477] [PMID: 32119961]
[20]
Elfiky AA. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study. Life Sci 2020; 253: 117592.
[http://dx.doi.org/10.1016/j.lfs.2020.117592] [PMID: 32222463]
[21]
Gao Y, Yan L, Huang Y, et al. Structure of RNA-dependent RNA polymerase from 2019-nCoV, a major antiviral drug target. Science 2020; 368(6492): 779-82.
[http://dx.doi.org/10.1126/science.abb7498] [PMID: 32277040]
[22]
Lung J, Lin YS, Yang YH, et al. The potential chemical structure of anti-SARS-CoV-2 RNA-dependent RNA polymerase. J Med Virol 2020; 92(6): 693-7.
[http://dx.doi.org/10.1002/jmv.25761] [PMID: 32167173]
[23]
Shah B, Modi P, Sagar SR. In silico studies on therapeutic agents for COVID-19: Drug repurposing approach. Life Sci 2020; 252: 117652.
[http://dx.doi.org/10.1016/j.lfs.2020.117652] [PMID: 32278693]
[24]
Ueda Y, Mori K, Satoh S, Dansako H, Ikeda M, Kato N. Anti-HCV activity of the Chinese medicinal fungus Cordyceps militaris. Biochem Biophys Res Commun 2014; 447(2): 341-5.
[http://dx.doi.org/10.1016/j.bbrc.2014.03.150] [PMID: 24726408]
[25]
Chanda SD, Banerjee A, Nandi S, Chakrabarti S, Sarkar MC. Cordycepin: an adenosine analogue executes anti rotaviral effect by stimulating induction of type I-interferon. J Virol Antivir Res 2015; 4: 2.
[http://dx.doi.org/10.4172/2324-8955.1000138]
[26]
Qiu XL, Xu XH, Qing FL. Recent advances in the synthesis of fluorinated nucleosides. Tetrahedron 2010; 66: 789-843.
[http://dx.doi.org/10.1016/j.tet.2009.11.001]
[27]
Seley-Radtke KL, Yates MK. The evolution of nucleoside analogue antivirals: A review for chemists and non-chemists. Part 1: Early structural modifications to the nucleoside scaffold. Antiviral Res 2018; 154: 66-86.
[http://dx.doi.org/10.1016/j.antiviral.2018.04.004] [PMID: 29649496]
[28]
Wu AM, Ting RC, Paran M, Gallo RC. Cordycepin inhibits induction of murine leukovirus production by 5-iodo-2′-deoxyuridine. Proc Natl Acad Sci USA 1972; 69(12): 3820-4.
[http://dx.doi.org/10.1073/pnas.69.12.3820] [PMID: 4118874]
[29]
Doetsch PW, Suhadolnik RJ, Sawada Y, et al. Core (2′-5′)oligoadenylate and the cordycepin analog: inhibitors of Epstein-Barr virus-induced transformation of human lymphocytes in the absence of interferon. Proc Natl Acad Sci USA 1981; 78(11): 6699-703.
[http://dx.doi.org/10.1073/pnas.78.11.6699] [PMID: 6171822]
[30]
Sawai H, Imai J, Lesiak K, Johnston MI, Torrence PF. Cordycepin analogues of 2-5A and its derivatives. Chemical synthesis and biological activity. J Biol Chem 1983; 258(3): 1671-7.
[http://dx.doi.org/10.1016/S0021-9258(18)33038-2] [PMID: 6296109]
[31]
Eppstein DA, Barnett JW, Marsh YV, Gosselin G, Imbach JL. Xyloadenosine analogue of (A2'p)2A inhibits replication of herpes simplex viruses 1 and 2. Nature 1983; 302(5910): 723-4.
[http://dx.doi.org/10.1038/302723a0] [PMID: 6300696]
[32]
Montefiori DC, Sobol RW Jr, Li SW, et al. Phosphorothioate and cordycepin analogues of 2′,5′-oligoadenylate: inhibition of human immunodeficiency virus type 1 reverse transcriptase and infection in vitro. Proc Natl Acad Sci USA 1989; 86(18): 7191-4.
[http://dx.doi.org/10.1073/pnas.86.18.7191] [PMID: 2476814]
[33]
Müller WE, Weiler BE, Charubala R, et al. Cordycepin analogues of 2′,5′-oligoadenylate inhibit human immunodeficiency virus infection via inhibition of reverse transcriptase. Biochemistry 1991; 30(8): 2027-33.
[http://dx.doi.org/10.1021/bi00222a004] [PMID: 1705437]
[34]
Marques VE, Lin BB, Barchi JJ, Nicklaus MC. Nucleosides and nucleotides as antitumor and antiviral agents. Springer US: Plenum Press 1993; pp. 265-84.
[35]
Ahluwalia GS, Cooney DA, Shirasaka T, Mitsuya H, Driscoll JS, Johns DG. Enhancement by 2′-deoxycoformycin of the 5′-phosphorylation and anti-human immunodeficiency virus activity of 2′,3′-dideoxyadenosine and 2′-beta-fluoro-2′,3′-dideoxyadenosine. Mol Pharmacol 1994; 46(5): 1002-8.
[PMID: 7969062]
[36]
Shimada H, Haraguchi K, Hotta K, et al. Synthesis of 3′,4′-difluoro-3′-deoxyribonucleosides and its evaluation of the biological activities: discovery of a novel type of anti-HCV agent 3′,4′-difluorocordycepin. Bioorg Med Chem 2014; 22(21): 6174-82.
[http://dx.doi.org/10.1016/j.bmc.2014.08.024] [PMID: 25282652]
[37]
Watling D, Serafinowska HT, Reese CB, Kerr IM. Analogue inhibitor of 2-5A action: effect on the interferon-mediated inhibition of encephalomyocarditis virus replication. EMBO J 1985; 4(2): 431-6.
[http://dx.doi.org/10.1002/j.1460-2075.1985.tb03647.x] [PMID: 2410258]
[38]
Park IH, Kwon YC, Ryu WS, Ahn BY. Inhibition of hepatitis B virus replication by ligand-mediated activation of RNase L. Antiviral Res 2014; 104: 118-27.
[http://dx.doi.org/10.1016/j.antiviral.2014.01.021] [PMID: 24509240]
[39]
Duhovny D, Nussinov R, Wolfson HJ. Efficient unbound docking of rigid molecules. In: Guigó R, Gusfield D, Eds. Proceedings of the 2'nd Workshop on Algorithms in Bioinformatics (WABI) Lecture notes in computer science. Rome, Italy: Springer Verlag 2002; 2452: pp. 185-200.
[http://dx.doi.org/10.1007/3-540-45784-4_14]
[40]
Zhang C, Vasmatzis G, Cornette JL, DeLisi C. Determination of atomic desolvation energies from the structures of crystallized proteins. J Mol Biol 1997; 267(3): 707-26.
[http://dx.doi.org/10.1006/jmbi.1996.0859] [PMID: 9126848]
[41]
Wang J, Liu R, Liu B, Yang Y, Xie J, Zhu N. Systems Pharmacology-based strategy to screen new adjuvant for hepatitis B vaccine from Traditional Chinese Medicine Ophiocordyceps sinensis. Sci Rep 2017; 7: 44788.
[http://dx.doi.org/10.1038/srep44788] [PMID: 28317886]
[42]
Wang Z. Pharmaceutical composition for treating AIDS and preparation method thereof. U.S. patent 9623053, 2017.
[43]
Yong T, Chen S, Xie Y, et al. Cordycepin, a characteristic bioactive constituent in Cordyceps militaris, Ameliorates Hyperuricemia through URAT1 in hyperuricemic mice. Front Microbiol 2018; 9: 58.
[http://dx.doi.org/10.3389/fmicb.2018.00058] [PMID: 29422889]
[44]
Wei HP, Ye XL, Chen Z, et al. Synthesis and pharmacokinetic evaluation of novel N-acyl-cordycepin derivatives with a normal alkyl chain. Eur J Med Chem 2009; 44(2): 665-9.
[http://dx.doi.org/10.1016/j.ejmech.2008.05.013] [PMID: 18599159]
[45]
Lee HJ, Burger P, Vogel M, Friese K, Brüning A. The nucleoside antagonist cordycepin causes DNA double strand breaks in breast cancer cells. Invest New Drugs 2012; 30(5): 1917-25.
[http://dx.doi.org/10.1007/s10637-012-9859-x] [PMID: 22821173]
[46]
Aramwit P, Bang N, Ratanavaraporn J, Nakpheng T, Srichana T. An anti-cancer cordycepin produced by Cordyceps militaris growing on the dead larva of Bombyx mori silkworm. J Agric Sci 2014; 6: 41-53.
[47]
Aramwit P, Porasuphatana S, Srichana T, Nakpheng T. Toxicity evaluation of cordycepin and its delivery system for sustained in vitro anti-lung cancer activity. Nanoscale Res Lett 2015; 10: 152.
[http://dx.doi.org/10.1186/s11671-015-0851-1] [PMID: 25883541]
[48]
Bi YE, Zhou Y, Wang M, et al. targeted delivery of cordycepin to liver cancer cells using transferrin-conjugated liposomes. Anticancer Res 2017; 37(9): 5207-14.
[http://dx.doi.org/10.21873/anticanres.11944] [PMID: 28870956]
[49]
Verma AK, Aggarwal R. Repurposing potential of FDA-approved and investigational drugs for COVID-19 targeting SARS-CoV-2 spike and main protease and validation by machine learning algorithm. Chem Biol Drug Des 2021; 97(4): 836-53.
[http://dx.doi.org/10.1111/cbdd.13812] [PMID: 33289334]

Rights & Permissions Print Cite
Article Metrics
20
2
© 2024 Bentham Science Publishers | Privacy Policy