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An in-silico investigation of volatile compounds in Tulsi and Ginger as a potent inhalant for SARS-CoV-2 treatment

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Abstract

The COVID-19 pandemic caused by SARS-CoV-2 still remains an interesting subject of study just as the exploration of natural compounds as therapeutic agents. The novelty of this work lies in an identification and exploration of active volatile compounds found in the herbal inhalants, which exhibit promising interactions with COVID-19 proteins. The 29 phytochemicals listed from various databases were evaluated for drug-likeness and ADMET properties. Their potential was evaluated through molecular docking with two well-studied protein targets, namely the spike protein (PDB ID: 6MOJ) and Mpro (PDB ID: 6LU7), which are involved in propagating infection. Compound 4: (1S,8aR)-1-isopropyl-4,7-dimethyl-1,2,3,5,6,8a-hexahydronaphthalene, and compound-22: (2E,6E,10E)-2,6,6,9-tetramethylcycloundeca-2,6,10-trien-1-one demonstrated robust binding affinities with these proteins, exhibiting binding energies of −7.6 and −7.4 kcal/mol for 6MOJ, and -5.8 and −6.2 kcal/mol for 6LU7. In detail analysis and validation for the selected phytochemicals was carried out by MM-GBSA, and Density Functional Theory (DFT) studies. These findings contribute to the exploration of natural compounds from the Indian medicinal herbs Tulsi and Ginger as potential therapeutic agents against COVID-19.

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References

  1. C. Wu, Y. Liu, Y. Yang, P. Zhang, W. Zhong, Y. Wang, H. Li, Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm. Sin. B 10(5), 766–788 (2020). https://doi.org/10.1016/j.apsb.2020.02.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. P. Zhou, X.L. Yang, X.G. Wang, B. Hu, L. Zhang, W. Zhang, Z.L. Shi, A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579(7798), 270–273 (2020). https://doi.org/10.1038/s41586-020-2012-7

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  3. M. Mahanthesh, D. Ranjith, R. Yaligar, R. Jyothi, G. Narappa, M. Ravi, Swiss ADME prediction of phytochemicals present in Butea monosperma (Lam.) Taub. J. Pharm. Phytochem. 9(3), 1799–1809 (2020)

    CAS  Google Scholar 

  4. S. Abdurrahman, R. Ruslin, A.N. Hasanah, R. Mustarichie, Molecular docking studies and ADME-Tox prediction of phytocompounds from Merremiapeltata as a potential anti-alopecia treatment. J. Adv. Pharm. Technol. Res. 12(2), 132 (2021). https://doi.org/10.4103/japtr.JAPTR_222_20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. A.S. Barros, A. Costa, B. Sarmento, Building three-dimensional lung models for studying pharmacokinetics of inhaled drugs. Adv. Drug Deliv. Rev. 170, 386–395 (2021). https://doi.org/10.1016/j.addr.2020.09.008

    Article  CAS  PubMed  Google Scholar 

  6. T. Pillaiyar, S. Meenakshisundaram, M. Manickam, Recent discovery and development of inhibitors targeting coronaviruses. Drug Discov. Today 25(4), 668–688 (2020). https://doi.org/10.1016/j.drudis.2020.01.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. H. Zhang, K.M. Saravanan, Y. Yang, M.T. Hossain, J. Li, X. Ren, Y. Wei, Deep learning based drug screening for novel coronavirus 2019-nCov. Interdiscip. Sci.: Comput. Life Sci. 12, 368–376 (2020). https://doi.org/10.1007/s12539-020-00376-6

    Article  CAS  Google Scholar 

  8. W. Hussain, K.S. Haleem, I. Khan, I. Tauseef, S. Qayyum, B. Ahmed, M.N. Riaz, Medicinal plants: a repository of antiviral metabolites. Futur. Virol. 12(6), 299–308 (2017). https://doi.org/10.2217/fvl-2016-0110

    Article  CAS  Google Scholar 

  9. M. Denaro, A. Smeriglio, D. Barreca, C. De Francesco, C. Occhiuto, G. Milano, D. Trombetta, Antiviral activity of plants and their isolated bioactive compounds: an update. Phytother. Res. 34(4), 742–768 (2020). https://doi.org/10.1002/ptr.6575

    Article  PubMed  Google Scholar 

  10. A.K. Srivastava, A. Kumar, H. Srivastava, N. Misra, The role of herbal plants in the inhibition of SARS-CoV-2 main protease: a computational approach. J. Indian Chem. Soc. 99(9), 100640 (2022). https://doi.org/10.1016/j.jics.2022.100640

    Article  CAS  Google Scholar 

  11. S.S. Ghoke, R. Sood, N. Kumar, A.K. Pateriya, S. Bhatia, A. Mishra, V.P. Singh, Evaluation of antiviral activity of Ocimum sanctum and Acacia arabica leaves extracts against H9N2 virus using embryonated chicken egg model. BMC Complement. Altern. Med. 18(1), 1–10 (2018). https://doi.org/10.1186/s12906-018-2238-1

    Article  CAS  Google Scholar 

  12. A. Kumar, Molecular docking of natural compounds from tulsi (Ocimum sanctum) and neem (Azadirachta indica) against SARS-CoV-2 protein targets. (2020). https://doi.org/10.21203/rs.3.rs-27151/v1.

  13. M.A. Nawwar, S.A.M. Hussein, I. Merfort, Leaf phenolics of some Ocimum species. Phytochemistry 37(1), 277–279 (1994). https://doi.org/10.1016/s0031-9422(00)89553-7

    Article  Google Scholar 

  14. M.S. Khan, I. Ahmad, Antibacterial efficacy of essential oil and various extracts of a medicinal plant against clinical and phytopathogenic bacteria. Pharm. Biol. 50(7), 850–857 (2012). https://doi.org/10.3109/13880209.2012.752737

    Article  Google Scholar 

  15. M. Nath, P. Debnath, Therapeutic role of traditionally used Indian medicinal plants and spices in combating COVID-19 pandemic situation. J. Biomol. Struct. Dyn. 41(12), 5894–5913 (2023). https://doi.org/10.1080/07391102.2022.2093793

    Article  CAS  PubMed  Google Scholar 

  16. M.H. Shahrajabian, W. Sun, Q. Cheng, Clinical aspects and health benefits of ginger (Zingiber officinale) in both traditional Chinese medicine and modern industry. Acta Agric. Scand. Sect. b Soil Plant Sci. 69(6), 546–556 (2019). https://doi.org/10.1080/09064710.2019.1606930

    Article  CAS  Google Scholar 

  17. H. Kikuzaki, T. Sasaki, M. Asahi et al., Gingerdione, a novel metabolite of ginger, suppresses pro-inflammatory cytokine production by inhibiting lipopolysaccharide-induced NF-κB activation. Food Funct. 4(2), 258–264 (2013). https://doi.org/10.1039/c2fo30219a

    Article  Google Scholar 

  18. Y.S. Lee, A.R. Han, S.K. Woo et al., Inhibitory effects of zingiberene and its derivatives against respiratory syncytial virus in vitro and in vivo. J. Agric. Food Chem. 62(45), 10573–10577 (2014). https://doi.org/10.1021/jf5031358

    Article  Google Scholar 

  19. S. Wang, C. Zhang, G. Yang, Y. Yang, Biological properties of gingerol: a brief review. Nat. Prod. Commun. 9(7), 1934578X1400900736 (2014). https://doi.org/10.1177/1934578X1400900736

    Article  Google Scholar 

  20. N.G. Dsouza, C. Mohammad Asif Iqbal, M.G. Ahmed, A review on the correlation of traditional plants used for antiviral therapy as a possible treatment for Covid-19. Manipal J. Pharm. Sci. 7(1), 10 (2021)

    Google Scholar 

  21. D. Kumar, P. Arya, some immunity-boosting plants used during the covid-19 pandemic to prevent corona virus infection in Kumaun Himalayan region of Uttarakhand, India. Plant Arch. 21(2), 510–517 (2021)

    Google Scholar 

  22. Z.A. Krumm, G.M. Lloyd, C.P. Francis, L.H. Nasif, D.A. Mitchell, T.E. Golde, Y. Xia, Precision therapeutic targets for COVID-19. Virol. J. 18(1), 1–22 (2021). https://doi.org/10.1186/s12985-021-01526-y

    Article  CAS  Google Scholar 

  23. C. Gil, T. Ginex, I. Maestro, V. Nozal, L. Barrado-Gil, M.Á. Cuesta-Geijo, A. Martinez, COVID-19: drug targets and potential treatments. J. Med. Chem. 63(21), 12359–12386 (2020). https://doi.org/10.1021/acs.jmedchem.0c00606

    Article  CAS  PubMed  Google Scholar 

  24. K. Raj, K. Kaur, G.D. Gupta, S. Singh, Current understanding on molecular drug targets and emerging treatment strategy for novel coronavirus-19. Naunyn-Schmiedeberg’s Arch. Pharmacol. 394(7), 1383–1402 (2021). https://doi.org/10.1007/s00210-021-02091-5

    Article  CAS  Google Scholar 

  25. A. Sternberg, C. Naujokat, Structural features of coronavirus SARS-CoV-2 spike protein: targets for vaccination. Life Sci. 257, 118056 (2020). https://doi.org/10.1016/j.lfs.2020.118056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Y. Huang, C. Yang, X.F. Xu, W. Xu, S.W. Liu, Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol. Sin. 41(9), 1141–1149 (2020). https://doi.org/10.1038/s41401-020-0485-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. B. Goyal, D. Goyal, Targeting the dimerization of the main protease of coronaviruses: a potential broad-spectrum therapeutic strategy. ACS Comb. Sci. 22(6), 297–305 (2020). https://doi.org/10.1021/acscombsci.0c00058

    Article  CAS  PubMed  Google Scholar 

  28. M. Kuroda, Y. Mimaki, T. Nishiyama, T. Mae, H. Kishida, M. Tsukagawa, K. Takahashi, T. Kawada, K. Nakagawa, M. Kitahara, Hypoglycemic effects of turmeric (Curcuma longa L. rhizomes) on genetically diabetic KK-Ay mice. Biol. Pharm. Bull. 28(5), 937–939 (2005). https://doi.org/10.1248/bpb.28.937

    Article  CAS  PubMed  Google Scholar 

  29. S. Li, W. Yuan, G. Deng, P. Wang, P. Yang, B. Aggarwal, Chemical composition and product quality control of turmeric (Curcuma longa L.). (2011). https://scholarworks.sfasu.edu/agriculture_facultypubs/1

  30. D.Y. Chen, J.H. Shien, L. Tiley, S.S. Chiou, S.Y. Wang, T.J. Chang, Y.J. Lee, K.W. Chan, W.L. Hsu, Curcumin inhibits influenza virus infection and haemagglutination activity. Food Chem. 119(4), 1346–1351 (2010). https://doi.org/10.1016/j.foodchem.2009.09.011

    Article  CAS  Google Scholar 

  31. B.B. Aggarwal, A. Kumar, A.C. Bharti, Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 23(1/A), 363–398 (2003)

    CAS  PubMed  Google Scholar 

  32. P. Prakash, A. Misra, W.R. Surin, M. Jain, R.S. Bhatta, R. Pal, K. Raj, M.K. Barthwal, M. Dikshit, Anti-platelet effects of Curcuma oil in experimental models of myocardial ischemia-reperfusion and thrombosis. Thromb. Res. 127(2), 111–118 (2011). https://doi.org/10.1016/j.thromres.2010.11.007

    Article  CAS  PubMed  Google Scholar 

  33. B. Gupta, B. Ghosh, Curcuma longa inhibits TNF-α induced expression of adhesion molecules on human umbilical vein endothelial cells. Int. J. Immunopharmacol. 21(11), 745–757 (1999). https://doi.org/10.1016/S0192-0561(99)00050-8

    Article  CAS  PubMed  Google Scholar 

  34. Y. Abe, S.H.U. Hashimoto, T. Horie, Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. Pharmacol. Res. 39(1), 41–47 (1999). https://doi.org/10.1006/phrs.1998.0404

    Article  CAS  PubMed  Google Scholar 

  35. D.S. Kim, S.Y. Park, J.Y. Kim, Curcuminoids from Curcuma longa L.(Zingiberaceae) that protect PC12 rat pheochromocytoma and normal human umbilical vein endothelial cells from βA (1–42) insult. Neurosci. Lett. 303(1), 57–61 (2001). https://doi.org/10.1016/S0304-3940(01)01677-9

    Article  CAS  PubMed  Google Scholar 

  36. V. Singh, R. Dayal, J.P. Bartley, Volatile constituents of Vitex negundo leaves. Planta Med. 65(06), 580–582 (1999). https://doi.org/10.1055/s-2006-960832

    Article  CAS  PubMed  Google Scholar 

  37. E. González-Burgos, M. Liaudanskas, J. Viškelis, V. Žvikas, V. Janulis, M.P. Gómez-Serranillos, Antioxidant activity, neuroprotective properties and bioactive constituents analysis of varying polarity extracts from Eucalyptus globulus leaves. J. Food Drug Anal. 26(4), 1293–1302 (2018). https://doi.org/10.1016/j.jfda.2018.05.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. S. Alagu Lakshmi, R.M.B. Shafreen, A. Priya, K.P. Shunmugiah, Ethnomedicines of Indian origin for combating COVID-19 infection by hampering the viral replication: using structure-based drug discovery approach. J. Biomol. Struct. Dyn. 39(13), 4594–4609 (2021). https://doi.org/10.1080/07391102.2020.1778537

    Article  CAS  PubMed  Google Scholar 

  39. R. Alexpandi, J.F. De Mesquita, S.K. Pandian, A.V. Ravi, Quinolines-based SARS-CoV-2 3CLpro and RdRp inhibitors and Spike-RBD-ACE2 inhibitor for drug-repurposing against COVID-19: an in silico analysis. Front. Microbiol. 11, 1796 (2020). https://doi.org/10.3389/fmicb.2020.01796

    Article  PubMed  PubMed Central  Google Scholar 

  40. R.S. Joshi, S.S. Jagdale, S.B. Bansode, S.S. Shankar, M.B. Tellis, V.K. Pandya, M.J. Kulkarni, Discovery of potential multi-target-directed ligands by targeting host-specific SARS-CoV-2 structurally conserved main protease. J. Biomol. Struct. Dyn. 39(9), 3099–3114 (2021). https://doi.org/10.1080/07391102.2020.1760137

    Article  CAS  PubMed  Google Scholar 

  41. Y. El Bakri, Y. Ramli, E.M. Essassi, J.T. Mague, Synthesis, crystal structure, spectroscopic characterization, Hirshfeld surface analysis, and DFT calculations of 1, 4-dimethyl-2-oxo-pyrimido [1, 2-a] benzimidazole hydrate. J. Mol. Struct. 1152, 154–162 (2018). https://doi.org/10.1016/j.molstruc.2017.09.074

    Article  ADS  CAS  Google Scholar 

  42. K.M. Chandini, F.H. Al-Ostoot, E.E. Shehata, N.Y. Elamin, H. Ferjani, M.A. Sridhar, N.K. Lokanath, Synthesis, crystal structure, Hirshfeld surface analysis, DFT calculations, 3D energy frameworks studies of Schiff base derivative 2, 2′-((1Z, 1′ Z)-(1, 2-phenylene bis (azanylylidene)) bis (methanylylidene)) diphenol. J. Mol. Struct. 1244, 130910 (2021). https://doi.org/10.1016/j.molstruc.2021.130910

    Article  CAS  Google Scholar 

  43. M. Usman, R.A. Khan, A. Alsalme, W. Alharbi, K.H. Alharbi, M.H. Jaafar, S. Tabassum, Structural, spectroscopic, and chemical bonding analysis of Zn (II) complex [Zn (sal)](H2O): combined experimental and theoretical (NBO, QTAIM, and ELF) investigation. Crystals 10(4), 259 (2020). https://doi.org/10.3390/cryst10040259

    Article  CAS  Google Scholar 

  44. A.G. Harrison, T. Lin, P. Wang, Mechanisms of SARS-CoV-2 transmission and pathogenesis. Trends Immunol. 41(12), 1100–1115 (2020). https://doi.org/10.1016/j.it.2020.10.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. W. Trypsteen, J. Van Cleemput, W.V. Snippenberg, S. Gerlo, L. Vandekerckhove, On the whereabouts of SARS-CoV-2 in the human body: a systematic review. PLoS Pathog. 16(10), e1009037 (2020). https://doi.org/10.1371/journal.ppat.1009037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. J. He, H. Tao, Y. Yan, S.Y. Huang, Y. Xiao, Molecular mechanism of evolution and human infection with SARS-CoV-2. Viruses 12(4), 428 (2020). https://doi.org/10.3390/v12040428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. M.Y. Wang, R. Zhao, L.J. Gao, X.F. Gao, D.P. Wang, J.M. Cao, SARS-CoV-2: structure, biology, and structure-based therapeutics development. Front. Cell. Infect. Microbiol. 10, 587269 (2020). https://doi.org/10.3389/fcimb.2020.587269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. A. Citarella, A. Scala, A. Piperno, N. Micale, SARS-CoV-2 Mpro: a potential target for peptidomimetics and small-molecule inhibitors. Biomolecules 11(4), 607 (2021). https://doi.org/10.3390/biom11040607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Q. Zhang, R. Xiang, S. Huo, Y. Zhou, S. Jiang, Q. Wang, F. Yu, Molecular mechanism of interaction between SARS-CoV-2 and host cells and interventional therapy. Signal Transduct. Target. Ther. 6(1), 233 (2021). https://doi.org/10.1038/s41392-021-00653-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. M.S. Nadeem, M.A. Zamzami, H. Choudhry, B.N. Murtaza, I. Kazmi, H. Ahmad, A.R. Shakoori, Origin, potential therapeutic targets and treatment for coronavirus disease (COVID-19). Pathogens 9(4), 307 (2020). https://doi.org/10.3390/pathogens9040307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. L.W. Shen, H.J. Mao, Y.L. Wu, Y. Tanaka, W. Zhang, TMPRSS2: a potential target for treatment of influenza virus and coronavirus infections. Biochimie 142, 1–10 (2017). https://doi.org/10.1016/j.biochi.2017.07.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. J. Bastida, R. Lavilla, F. Viladomat, Chemical and biological aspects of Narcissus alkaloids. Alkaloids Chem. Biol. 63, 87–179 (2006)

    Article  CAS  PubMed  Google Scholar 

  53. A. Balkrishna, S. Haldar, H. Singh, P. Roy, A. Varshney, Coronil, a tri-herbal formulation, attenuates spike-protein-mediated SARS-CoV-2 entry viral into human alveolar epithelial cells and pro-inflammatory cytokines production by inhibiting spike protein-ACE-2 interaction. J. Inflamm. Res. 14, 869 (2021)

    Article  PubMed  PubMed Central  Google Scholar 

  54. S. Bharadwaj, A. Dubey, U. Yadava, S.K. Mishra, S.G. Kang, V.D. Dwivedi, Exploration of natural compounds with anti-SARS-CoV-2 activity via inhibition of SARS-CoV-2 Mpro. Brief. Bioinform. 22(2), 1361–1377 (2021)

    Article  CAS  PubMed  Google Scholar 

  55. A. Vektariene, G. Vektaris, & J. Svoboda, A theoretical approach to the nucleophilic behavior of benzofused thieno [3, 2-b] furans using DFT and HF based reactivity descriptors. Arkivoc: Online Journal of Organic Chemistry. (2009)

  56. T. Akaike, Role of free radicals in viral pathogenesis and mutation. Rev. Med. Virol. 11(2), 87–101 (2001)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors are thankful to SJCE, JSS Science and Technology University for providing supercomputing facilities and instrumental facilities from the VGST-CISEE Project (GRD 647), GOK, and Karnataka. Researcher supported project number (RSP-2023R354) King Saud University, Riyadh, Saudi Arabia for support.

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  1. Department of Chemistry, SJCE, JSS Science and Technology University, Mysuru, Karnataka, 570 006, India

    J. Jayashankar, G. N. Ningaraju, S. Nanjundaswamy, C. S. Karthik & P. Mallu

  2. Department of Chemistry, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia

    Jothi Ramalingam Rajabathar

  3. Grassland and Forage Division, Rural Development Administration, National Institute of Animal Science, Cheonan, 31000, Chungcheongnam-do, Korea

    Muthusamy Karnan

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Jayashankar, J., Ningaraju, G.N., Nanjundaswamy, S. et al. An in-silico investigation of volatile compounds in Tulsi and Ginger as a potent inhalant for SARS-CoV-2 treatment. J IRAN CHEM SOC 21, 479–502 (2024). https://doi.org/10.1007/s13738-023-02939-y

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