Genomics & Informatics

Korea Genome Organization (한국유전체학회)
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Druggability for COVID-19: in silico discovery of potential drug compounds against nucleocapsid (N) protein of SARS-CoV-2

  • Received : 2020.09.07
  • Accepted : 2020.10.20
  • Published : 2020.12.31
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Abstract

The coronavirus disease 2019 is a contagious disease and had caused havoc throughout the world by creating widespread mortality and morbidity. The unavailability of vaccines and proper antiviral drugs encourages the researchers to identify potential antiviral drugs to be used against the virus. The presence of RNA binding domain in the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be a potential drug target, which serves multiple critical functions during the viral life cycle, especially the viral replication. Since vaccine development might take some time, the identification of a drug compound targeting viral replication might offer a solution for treatment. The study analyzed the phylogenetic relationship of N protein sequence divergence with other 49 coronavirus species and also identified the conserved regions according to protein families through conserved domain search. Good structural binding affinities of a few natural and/or synthetic phytocompounds or drugs against N protein were determined using the molecular docking approaches. The analyzed compounds presented the higher numbers of hydrogen bonds of selected chemicals supporting the drug-ability of these compounds. Among them, the established antiviral drug glycyrrhizic acid and the phytochemical theaflavin can be considered as possible drug compounds against target N protein of SARS-CoV-2 as they showed lower binding affinities. The findings of this study might lead to the development of a drug for the SARS-CoV-2 mediated disease and offer solution to treatment of SARS-CoV-2 infection.

Keywords

Acknowledgement

We are thankful to Dr. Pawan Kumar Agrawal, Vice chancellor, Odisha University of Agriculture and Technology for his moral support and valuable suggestions.

References

  1. Adhikari SP, Meng S, Wu YJ, Mao YP, Ye RX, Wang QZ, et al. Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: a scoping review. Infect Dis Poverty 2020;9:29. https://doi.org/10.1186/s40249-020-00646-x
  2. Jiang S, Hillyer C, Du L. Neutralizing antibodies against SARSCoV-2 and other human coronaviruses. Trends Immunol 2020;41:355-359. https://doi.org/10.1016/j.it.2020.03.007
  3. Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun 2020;11:1620. https://doi.org/10.1038/s41467-020-15562-9
  4. Wang Q, Zhang Y, Wu L, Niu S, Song C, Zhang Z, et al. Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell 2020;181:894-904. https://doi.org/10.1016/j.cell.2020.03.045
  5. McBride R, van Zyl M, Fielding BC. The coronavirus nucleocapsid is a multifunctional protein. Viruses 2014;6:2991-3018. https://doi.org/10.3390/v6082991
  6. Yang P, Wang X. COVID-19: a new challenge for human beings. Cell Mol Immunol 2020;17:555-557. https://doi.org/10.1038/s41423-020-0407-x
  7. Lin SM, Lin SC, Hsu JN, Chang CK, Chien CM, Wang YS, et al. Structure-based stabilization of non-native protein-protein interactions of coronavirus nucleocapsid proteins in antiviral drug design. J Med Chem 2020;63:3131-3141. https://doi.org/10.1021/acs.jmedchem.9b01913
  8. Kumar S, Stecher G, Tamura K. MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol 2016;33:1870-1874. https://doi.org/10.1093/molbev/msw054
  9. Marchler-Bauer A, Anderson JB, Derbyshire MK, DeWeese-Scott C, Gonzales NR, Gwadz M, et al. CDD: a conserved domain database for interactive domain family analysis. Nucleic Acids Res 2007;35:D237-D240. https://doi.org/10.1093/nar/gkl951
  10. Buchan DW, Jones DT. The PSIPRED Protein Analysis Workbench: 20 years on. Nucleic Acids Res 2019;47:W402-W407. https://doi.org/10.1093/nar/gkz297
  11. Huang B. MetaPocket: a meta approach to improve protein ligand binding site prediction. OMICS 2009;13:325-330. https://doi.org/10.1089/omi.2009.0045
  12. Rizvi SM, Shakil S, Haneef M. A simple click by click protocol to perform docking: AutoDock 4.2 made easy for non-bioinformaticians. EXCLI J 2013;12:831-857.
  13. Fuhrmann J, Rurainski A, Lenhof HP, Neumann D. A new Lamarckian genetic algorithm for flexible ligand-receptor docking. J Comput Chem 2010;31:1911-1918.
  14. Bogusz M, Whelan S. Phylogenetic tree estimation with and without alignment: new distance methods and benchmarking. Syst Biol 2017;66:218-231.
  15. Sahoo M, Jena L, Rath SN, Kumar S. Identification of suitable natural inhibitor against influenza A (H1N1) neuraminidase protein by molecular docking. Genomics Inform 2016;14:96-103. https://doi.org/10.5808/GI.2016.14.3.96
  16. Moghadamtousi SZ, Kadir HA, Hassandarvish P, Tajik H, Abubakar S, Zandi K. A review on antibacterial, antiviral, and antifungal activity of curcumin. Biomed Res Int 2014;2014:186864.
  17. Ashfaq UA, Idrees S. Medicinal plants against hepatitis C virus. World J Gastroenterol 2014;20:2941-2947. https://doi.org/10.3748/wjg.v20.i11.2941
  18. Mohan M, James P, Valsalan R, Nazeem PA. Molecular docking studies of phytochemicals from Phyllanthus niruri against hepatitis B DNA polymerase. Bioinformation 2015;11:426-431. https://doi.org/10.6026/97320630011426
  19. Doki T, Tarusawa T, Hohdatsu T, Takano T. In vivo antiviral effects of U18666A against type I feline infectious peritonitis virus. Pathogens 2020;9:67. https://doi.org/10.3390/pathogens9010067
  20. Alhazmi MI. Molecular docking of selected phytocompounds with H1N1 proteins. Bioinformation 2015;11:196-202. https://doi.org/10.6026/97320630011196
  21. Rafe T, Shawon PA, Salem L, Chowdhury NI, Kabir F, Bin Zahur SM, et al. Preventive role of resveratrol against inflammatory cytokines and related diseases. Curr Pharm Des 2019;25:1345-1371. https://doi.org/10.2174/1381612825666190410153307
  22. Kaliyaperumal S, Periyasamy K, Balakrishnan U, Palanivel P, Egbuna C. Antiviral phytocompounds for drug development: a data mining studies. In: Phytochemicals as Lead Compounds for New Drug Discovery (Egbuna C, Kumar S, Ifemeje J, Ezzat S, Kaliyaperumal S, eds.). Amsterdam: Elsevier, 2020. pp. 239-244.
  23. Chen F, Chan KH, Jiang Y, Kao RY, Lu HT, Fan KW, et al. In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J Clin Virol 2004;31:69-75.
  24. Ho TY, Wu SL, Chen JC, Li CC, Hsiang CY. Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction. Antiviral Res 2007;74:92-101. https://doi.org/10.1016/j.antiviral.2006.04.014
  25. Jagadeb M, Rath SN, Sonawane A. In silico discovery of potential drug molecules to improve the treatment of isoniazid-resistant Mycobacterium tuberculosis. J Biomol Struct Dyn 2019;37: 3388-3398. https://doi.org/10.1080/07391102.2018.1515116
  26. Kadioglu O, Saeed M, Johannes Greten H, Efferth T. Identification of novel compounds against three targets of SARS CoV-2 coronavirus by combined virtual screening and supervised machine learning. Preprint at http://dx.doi.org/10.2471/BLT.20.255943 (2020).
  27. Calligari P, Bobone S, Ricci G, Bocedi A. Molecular investigation of SARS-CoV-2 proteins and their interactions with antiviral drugs. Viruses 2020;12:445. https://doi.org/10.3390/v12040445
  28. Sarma P, Shekhar N, Prajapat M, Avti P, Kaur H, Kumar S, et al. In-silico homology assisted identification of inhibitor of RNA binding against 2019-nCoV N-protein (N terminal domain). J Biomol Struct Dyn 2020 May 18 [Epub]. https://doi.org/10.1080/07391102.2020.1753580.
  29. Bhowmik D, Nandi R, Jagadeesan R, Kumar N, Prakash A, Kumar D. Identification of potential inhibitors against SARS-CoV-2 by targeting proteins responsible for envelope formation and virion assembly using docking based virtual screening, and pharmacokinetics approaches. Infect Genet Evol 2020;84:104451. https://doi.org/10.1016/j.meegid.2020.104451
  30. Kang S, Yang M, Hong Z, Zhang L, Huang Z, Chen X, et al. Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites. Acta Pharm Sin B 2020;10:1228-1238. https://doi.org/10.1016/j.apsb.2020.04.009
  31. Johns C. Glycyrrhizic acid toxicity caused by consumption of licorice candy cigars. CJEM 2009;11:94-96. https://doi.org/10.1017/S1481803500010988
  32. Chen R, Lin J, Hong J, Han D, Zhang AD, Lan R, et al. Potential toxicity of quercetin: the repression of mitochondrial copy number via decreased POLG expression and excessive TFAM expression in irradiated murine bone marrow. Toxicol Rep 2014;1:450-458. https://doi.org/10.1016/j.toxrep.2014.07.014