Covid-19 Research

Short Communication

Revisiting and Updating Cyanorona-20: The Selective SARS-CoV-2 Inhibitor

Journal of Biomedical Research & Environmental Sciences article abstract with citation details, DOI, publication dates, subject areas, full text links, and references.

View DOI Submit Manuscript

Article Details

Publication record, authors, dates, abstract, and full text access.

Open Access
Article Type Short Communication
Subject Medicine Group
OCLC 9506577152
Amgad M. Rabie*
Issue: Volume3-Issue4
Pages: 477-484
Received: 2022-03-18
Accepted: 2022-04-28
Published: 2022-04-30

Abstract

Evident inhibition/blockade of the viral RNA-dependent RNA polymerase (RdRp) of the newly-emerged fatal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is considered one of the most promising and efficient approaches for developing highly potent remedies for Coronavirus Disease 2019 (COVID-19). However, almost all of the reported viral RdRp inhibitors (either repurposed or new antiviral drugs) lack specific selectivity against the novel coronaviral-2 RdRp and still at a beginning phase of advancement. In this complementary research study, the new pyrazine derivative cyanorona-20 was revisited with an update about its synthetic and toxicological data. This promising selective specific anti-COVID-19 compound is deemed to be the first distinctive derivative of favipiravir. Cyanorona-20, the unrivalled nucleoside/nucleotide analog, was designed, synthesized, characterized, computationally studied, and biologically evaluated for its anti-COVID-19/cytotoxic actions. The results of the biological assay displayed that cyanorona-20 surprisingly exhibited very high and largely significant anti-COVID-19 activities (anti-SARS-CoV-2 EC50 = 0.45 μM), and, in addition, it could be also a very promising guide and lead compound for the design and synthesis of new anti-SARS-CoV-2 and anti-COVID-19 agents through structural modifications and further computational studies. Further appraisal for the improvement of cyanorona-20 medication, through performing deeper in vivo biological evaluations and extensive clinical trials, is a prerequisite requirement in the coming days. In this short communication paper, the comprehensive chemicobiological data and information about the "Corona Antidote", cyanorona-20 compound, were briefly and collectively revisited and the synthetic and pharmacotoxicological data were updated.

FullText HTML FullText PDF DOI: 10.37871/jbres1468 Crossmark

Certificate of Publication

Certificate of Publication

Copyright

© 2022 Rabie AM. Distributed under Creative Commons CC-BY 4.0 Creative CommonsAttribution

How to cite this article

Rabie AM. Revisiting and Updating Cyanorona-20: The Selective SARS-CoV-2 Inhibitor. J Biomed Res Environ Sci. 2022 Apr 30; 3(4): 477-484. doi: 10.37871/jbres1468, Article ID: JBRES1468, Available at: https://www.jelsciences.com/articles/ jbres1468.pdf

Subject area(s)

Pharmacology

References

  1. Hui DS, I Azhar E, Madani TA, Ntoumi F, Kock R, Dar O, Ippolito G, Mchugh TD, Memish ZA, Drosten C, Zumla A, Petersen E. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health - The latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis. 2020 Feb;91:264-266. doi: 10.1016/j.ijid.2020.01.009. Epub 2020 Jan 14. PMID: 31953166; PMCID: PMC7128332.
  2. Li JY, You Z, Wang Q, Zhou ZJ, Qiu Y, Luo R, Ge XY. The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future. Microbes Infect. 2020 Mar;22(2):80-85. doi: 10.1016/j.micinf.2020.02.002. Epub 2020 Feb 20. PMID: 32087334; PMCID: PMC7079563.
  3. Jiang S, Du L, Shi Z. An emerging coronavirus causing pneumonia outbreak in Wuhan, China: calling for developing therapeutic and prophylactic strategies. Emerg Microbes Infect. 2020 Jan 31;9(1):275-277. doi: 10.1080/22221751.2020.1723441. Erratum in: Emerg Microbes Infect. 2020 Dec;9(1):539. PMID: 32005086; PMCID: PMC7033706.
  4. Shiraki K, Daikoku T. Favipiravir, an anti-influenza drug against life-threatening RNA virus infections. Pharmacol Ther. 2020 May;209:107512. doi: 10.1016/j.pharmthera.2020.107512. Epub 2020 Feb 22. PMID: 32097670; PMCID: PMC7102570.
  5. Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov Ther. 2020;14(1):58-60. doi: 10.5582/ddt.2020.01012. PMID: 32147628.
  6. Venkataraman S, Prasad BVLS, Selvarajan R. RNA Dependent RNA Polymerases: Insights from Structure, Function and Evolution. Viruses. 2018 Feb 10;10(2):76. doi: 10.3390/v10020076. PMID: 29439438; PMCID: PMC5850383.
  7. Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y, Wang Q, Xu Y, Li M, Li X, Zheng M, Chen L, Li H. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm Sin B. 2020 May;10(5):766-788. doi: 10.1016/j.apsb.2020.02.008. Epub 2020 Feb 27. PMID: 32292689; PMCID: PMC7102550.
  8. Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral Res. 2013 Nov;100(2):446-54. doi: 10.1016/j.antiviral.2013.09.015. Epub 2013 Sep 29. PMID: 24084488; PMCID: PMC3880838.
  9. Smee DF, Hurst BL, Egawa H, Takahashi K, Kadota T, Furuta Y. Intracellular metabolism of favipiravir (T-705) in uninfected and influenza A (H5N1) virus-infected cells. J Antimicrob Chemother. 2009 Oct;64(4):741-6. doi: 10.1093/jac/dkp274. Epub 2009 Jul 29. PMID: 19643775; PMCID: PMC2740635.
  10. Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, Liao X, Gu Y, Cai Q, Yang Y, Shen C, Li X, Peng L, Huang D, Zhang J, Zhang S, Wang F, Liu J, Chen L, Chen S, Wang Z, Zhang Z, Cao R, Zhong W, Liu Y, Liu L. Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study. Engineering (Beijing). 2020 Oct;6(10):1192-1198. doi: 10.1016/j.eng.2020.03.007. Epub 2020 Mar 18. PMID: 32346491; PMCID: PMC7185795.
  11. Yoon JJ, Toots M, Lee S, Lee ME, Ludeke B, Luczo JM, Ganti K, Cox RM, Sticher ZM, Edpuganti V, Mitchell DG, Lockwood MA, Kolykhalov AA, Greninger AL, Moore ML, Painter GR, Lowen AC, Tompkins SM, Fearns R, Natchus MG, Plemper RK. Orally Efficacious Broad-Spectrum Ribonucleoside Analog Inhibitor of Influenza and Respiratory Syncytial Viruses. Antimicrob Agents Chemother. 2018 Jul 27;62(8):e00766-18. doi: 10.1128/AAC.00766-18. PMID: 29891600; PMCID: PMC6105843.
  12. Abdelnabi R, Morais ATS, Leyssen P, Imbert I, Beaucourt S, Blanc H, Froeyen M, Vignuzzi M, Canard B, Neyts J, Delang L. Understanding the Mechanism of the Broad-Spectrum Antiviral Activity of Favipiravir (T-705): Key Role of the F1 Motif of the Viral Polymerase. J Virol. 2017 May 26;91(12):e00487-17. doi: 10.1128/JVI.00487-17. PMID: 28381577; PMCID: PMC5446660.
  13. Du YX, Chen XP. Favipiravir: Pharmacokinetics and Concerns About Clinical Trials for 2019-nCoV Infection. Clin Pharmacol Ther. 2020 Aug;108(2):242-247. doi: 10.1002/cpt.1844. Epub 2020 Apr 21. PMID: 32246834.
  14. Rabie AM. Discovery of (E)-N-(4-cyanobenzylidene)- 6-fluoro- 3-hydroxypyrazine-2 -carboxamide (cyanorona-20): the first potent and specific anti-COVID-19 drug. Chem Zvesti. 2021 May 16:1-17. doi: 10.1007/s11696-021-01640-9. Epub ahead of print. PMID: 34025012; PMCID: PMC8126404.
  15. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):3-26. doi: 10.1016/s0169-409x(00)00129-0. PMID: 11259830.
  16. Ertl P, Rohde B, Selzer P. Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. J Med Chem. 2000 Oct 5;43(20):3714-7. doi: 10.1021/jm000942e. PMID: 11020286.
  17. Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem. 2002 Jun 6;45(12):2615-23. doi: 10.1021/jm020017n. PMID: 12036371.
  18. Jin Z, Smith LK, Rajwanshi VK, Kim B, Deval J. The ambiguous base-pairing and high substrate efficiency of T-705 (Favipiravir) Ribofuranosyl 5'-triphosphate towards influenza A virus polymerase. PLoS One. 2013 Jul 10;8(7):e68347. doi: 10.1371/journal.pone.0068347. PMID: 23874596; PMCID: PMC3707847.
  19. Baranovich T, Wong SS, Armstrong J, Marjuki H, Webby RJ, Webster RG, Govorkova EA. T-705 (favipiravir) induces lethal mutagenesis in influenza A H1N1 viruses in vitro. J Virol. 2013 Apr;87(7):3741-51. doi: 10.1128/JVI.02346-12. Epub 2013 Jan 16. PMID: 23325689; PMCID: PMC3624194.
  20. Furuta Y, Takahashi K, Shiraki K, Sakamoto K, Smee DF, Barnard DL, Gowen BB, Julander JG, Morrey JD. T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections. Antiviral Res. 2009 Jun;82(3):95-102. doi: 10.1016/j.antiviral.2009.02.198. Epub 2009 Mar 6. PMID: 19428599; PMCID: PMC7127082.
  21. Shannon A, Le NT, Selisko B, Eydoux C, Alvarez K, Guillemot JC, Decroly E, Peersen O, Ferron F, Canard B. Remdesivir and SARS-CoV-2: Structural requirements at both nsp12 RdRp and nsp14 Exonuclease active-sites. Antiviral Res. 2020 Jun;178:104793. doi: 10.1016/j.antiviral.2020.104793. Epub 2020 Apr 10. PMID: 32283108; PMCID: PMC7151495.
  22. Xue J, Moyer A, Peng B, Wu J, Hannafon BN, Ding WQ. Chloroquine is a zinc ionophore. PLoS One. 2014 Oct 1;9(10):e109180. doi: 10.1371/journal.pone.0109180. PMID: 25271834; PMCID: PMC4182877.
  23. Dabbagh-Bazarbachi H, Clergeaud G, Quesada IM, Ortiz M, O'Sullivan CK, Fernández-Larrea JB. Zinc ionophore activity of quercetin and epigallocatechin-gallate: from Hepa 1-6 cells to a liposome model. J Agric Food Chem. 2014 Aug 13;62(32):8085-93. doi: 10.1021/jf5014633. Epub 2014 Jul 31. PMID: 25050823.
  24. Rabie AM. CoViTris2020 and ChloViD2020: a striking new hope in COVID-19 therapy. Mol Divers. 2021 Aug;25(3):1839-1854. doi: 10.1007/s11030-020-10169-0. Epub 2021 Jan 3. PMID: 33389560; PMCID: PMC7778709.
  25. Ishida T. Review on the role of Zn2+ ions in viral pathogenesis and the effect of Zn2+ ions for host cell-virus growth inhibition. Am J Biomed Sci Res. 2019;2(1):28–37. doi: 10.34297/AJBSR.2019.02.000566
  26. Yin W, Mao C, Luan X, Shen DD, Shen Q, Su H, Wang X, Zhou F, Zhao W, Gao M, Chang S, Xie YC, Tian G, Jiang HW, Tao SC, Shen J, Jiang Y, Jiang H, Xu Y, Zhang S, Zhang Y, Xu HE. Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science. 2020 Jun 26;368(6498):1499-1504. doi: 10.1126/science.abc1560. Epub 2020 May 1. PMID: 32358203; PMCID: PMC7199908.
  27. te Velthuis AJ, van den Worm SH, Sims AC, Baric RS, Snijder EJ, van Hemert MJ. Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog. 2010 Nov 4;6(11):e1001176. doi: 10.1371/journal.ppat.1001176. PMID: 21079686; PMCID: PMC2973827.
  28. Derwand R, Scholz M. Does zinc supplementation enhance the clinical efficacy of chloroquine/hydroxychloroquine to win today's battle against COVID-19? Med Hypotheses. 2020 Sep;142:109815. doi: 10.1016/j.mehy.2020.109815. Epub 2020 May 6. PMID: 32408070; PMCID: PMC7202847.
  29. Guo Q, Xu M, Guo S, Zhu F, Xie Y, Shen J. The complete synthesis of favipiravir from 2-aminopyrazine. Chem. 2019. doi: 10.1007/s11696-018-0654-9
  30. ProTox-II Virtual Laboratory. 2022.
  31. Miniyar PB, Murumkar PR, Patil PS, Barmade MA, Bothara KG. Unequivocal role of pyrazine ring in medicinally important compounds: a review. Mini Rev Med Chem. 2013 Oct;13(11):1607-25. doi: 10.2174/1389557511313110007. PMID: 23544468.
  32. Molinspiration Web-based Software, Molinspiration Cheminformatics (Homepage on the Internet), Nova ulica, SK-900 26 Slovensky Grob, Slovak Republic, 2021; Available from Molinspiration Cheminformatics on the Web (homepage:
  33. http://www.molinspiration.com)
  34. ; Estimations were calculated through using Molinspiration Property Engine (Version 2021.10; Molinspiration Calculation of Molecular Properties) on this website (accessed and cited in 2021, 20–30 December).
  35. Ghose AK, Viswanadhan VN, Wendoloski JJ. A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. J Comb Chem. 1999 Jan;1(1):55-68. doi: 10.1021/cc9800071. PMID: 10746014.
Publish with JBRES — Peer-reviewed, multidisciplinary Open Access with rapid review, DOI, and global visibility.
Double-Blind CrossRef DOI Discoverable
Submit Manuscript Membership