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Targeting H3N2 Influenza Virus RNA-dependent RNA Polymerase by Using Bioactives from Essential Oils from Eucalyptus polybrachtea, Cymbopogon citratus and Cymbopogon khasianus
Abstract
A dramatic surge of H3N2 influenza virus is of grave concern worldwide and particularly in India. H3N2 cause acute respiratory infection, however, a few drugs are available for its mitigation. Subsequently, researchers have been involved in efforts to discover novel antiviral mechanisms that can lay the basis for new anti-influenza drugs. Influenza virus RNA-dependent RNA polymerase (RdRP) is a multi-functional hetero-trimer, implicated in the production of viral mRNA, hence plays a major role in viral infectivity thus directly associated with survival of the virus. RdRP have been cited as anappropriate target for therapeutic drug design. In the present study molecular docking was designed to estimate the effect of potent bioactive moleculesfrom essential oils from Eucalyptus polybrachtea (eucalyptus oil, EO), Cymbopogon citratus (lemon grass essential oil, LEO) and Cymbopogon khasianus (palmarosa essential oil, PEO) against RdRP protein. GC-FID (gas chromatography with flame-ionization detection) based composition profile, and in-silico docking study was conducted by using CB-dock 2 analysis followed by 2D interactions. GC-FID revealed eucalyptol, geranial and geraniolas major phytocompounds in EO, LEO and PEO respectively. The docking score indicated effective binding of ligands to RdRP. Interactions results indicated that, RdRP/ligand complexes form hydrogen, van der waals forces, pi-alkyl, alkyl, and pi-Sigma interactions. Based on above findings of aroma profile and docking, therefore, it was recommended that essential oils from above mentioned aromatic cropsmay represent potential herbal treatment to mitigate H3N2 infections.
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Abraham, D.J. (2003). Burger’s Medicinal Chemistry and Drug Discovery Volume 5: Chemotherapeutic Agents.
Agnish, S., Sharma, A.D., Kaur, I. (2022). Underutilized plant Cymbopogon pendulus derived essential oil is excellent source of bioactives with diverse biological activities. Rusian Agric Research,48,55-68
Barcellos, M.P., Santos, C.B., Federico, L.B., Almeida, P.F., da Silva, C.H.T.P., Taft, C.A. (2019). Pharmacophore and structure-based drug design, molecular dynamics and admet/tox studies to design novel potential pad4 inhibitors. J Biomol. Struc.t Dyn. 37:966–981
Bhatnagar, A. (2018). Composition variation of essential oil of Cymbopogon spp. growing in Garhwal region of Uttarakhand, India. J. App. Nat. Sci 10: 363–366.
Biswal, A.R., Venkataraghavan, R., Pazhamalai, V., Romauld, S. (2019). Molecular docking of various bioactive compounds from essential oil of Trachyaspermumammi against the fungal enzyme Candidapepsin-1. J Applied Pharma Sci. 9: 21-32.
Castiello, L., Seladi-Schulman, J. (2021). https://www.healthline.com/health/h3n2
Deyde, V.M., Xu, X., Bright, R.A., Shaw, M., Smith, C.B., Zhang, Y., Shu, Y., Gubareva, L.V., Cox, N.J., Klimov, A.I. (2007) Surveillance of Resistance to Adamantanes among Influenza A(H3N2) and A(H1N1) Viruses Isolated Worldwide. J. Infect. Dis. 196:249–257
Dutta, S., Munda, S., Chikkaputtaiah, C., Lal, M. (2017). Assessment of selection criteria for development of high yielding genotypes using variability parameters in lemon grass Cymbopogon flexuosus L. J. Ess. Oil Bearing Plants 20: 1450-1460.
Elaissi, A., Bel Haj Salah, K., Mabrouk, S., Chemli, R., Harzallah-Skhiri, F. (2011). Antibacterial activity and chemical composition of 20 Eucalyptus species essential oils. Food Chem, 129,1427–1434
Hussain, M., Galvin, H.D., Haw, T.Y., Nutsford, A.N., Husain, M. (2017) Drug resistance in influenza A virus: The epidemiology and management. Infect. Drug Resist. 10:121–134. doi: 10.2147/IDR.S105473
Jester, B.J., Uyeki, T.M., Jernigan, D.B. (2020). Fifty Years of Influenza A(H3N2) Following the Pandemic of 1968. Am J Public Health. 2020 May;110:669-676.
Jin, Z., Wang, Y., Yu, X.-F., Tan, Q.-Q., Liang, S.-S., Li, T., Zhang, H., Shaw, P.-C., Wang, J., Hu, C. (2020) Structure-based virtual screening of influenza virus RNA polymerase inhibitors from natural compounds: Molecular dynamics simulation and MM-GBSA calculation. Comput. Biol. Chem. 85:107241.
Jnanesha, A.C., Ashish, K., Singh, M.K., Nagaraj, S. (2019). Variation in the Essential Oil Yield and Chemical Composition of Palmarosa Biomass Cymbopogon martini (Roxb.) wats. var. Motia Burk) Under Different Location in Semi Arid Tropic Regions of India, Ind. J. Pure App. Biosci. 7: 107- 113.
Khan, T., Dixit, S., Ahmad, R. (2017). Molecular docking, PASS analysis, bioactivity score prediction, synthesis, characterization and biological activity evaluation of a functionalized 2-butanone thiosemicarbazone ligand and its complexes. J. Chem. Biol. 10: 91–104
Khanuja, S.P.S., Shasany, A.K., Pawar, A., Lal, R.K., Darokar, M.P., Naqvi, A.A., Raj Kumar, S., Sundaresan, V., Lal, N., Kumar, S. (2005). Essential oil constituents and RAPD markers to establish species relationship in Cymbopogon Spreng. (Poaceae), Biochem. Syst. Ecol. 33: 171-186
Konig, J., Muller, F. (2013) Transporters and drug-drug interactions: Important determinants of drug disposition and effects. Pharmacol Rev.65:944-66
Kushwaha, N., Chandra, S., Singh, C., Pharmacy, K., Puramufit, K., Kesharwani, P.U. (2018) A review on therapeutics application of Eucalyptus oil. Int. J. Herbal Med. 6:110-115
Leung, Y.-H., To, M.-K., Lam, T.-S., Yau, S.-W., Leung, O.-S., Chuang, S.-K. Epidemiology of human influenza A(H7N9) infection in Hong Kong. J. Microbiol. Immunol. Infect. 2017;50:183–188.
Lima, S.L., Colombo, A.L. de Almeida Junior, J.N. (2019). Fungal Cell Wall: Emerging Antifungals and Drug Resistance. Front. Microbiol. 10:2573
Liu, Z., Zhao, J., Li, W. et al. (2016) Computational screen and experimental validation of anti-influenza effects of quercetin and chlorogenic acid from traditional Chinese medicine. Sci Rep 6, 19095.
Liu, Z., Zhao, J., Li, W. (2016). Computational screen and experimental validation of anti-influenza effects of quercetin and chlorogenic acid from traditional Chinese medicine. Sci Rep 6, 19095.
Massari, S., Goracci, L., Desantis, J., Tabarrini, O. (2016) Polymerase Acidic Protein–Basic Protein 1 (PA–PB1) Protein–Protein Interaction as a Target for Next-Generation Anti-influenza Therapeutics. J. Med. Chem. 59:7699–7718
Poole, E.L., Medcalf, L., Elton, D., Digard, P. (2007) Evidence that the C-terminal PB2-binding region of the influenza A virus PB1 protein is a discrete ?-helical domain. FEBS Lett. 581:5300–5306.
Prashar, A., Hili, P., Veness, R.G., Evans, C.S. (2003). Antimicrobial action of palmarosa oil (Cymbopogon martinii) on Saccharomyces cerevisiae. Phytochemistry 5:569-75.
Raho, G.B., Benali, M. (2012). Antibacterial activity of the essential oils from the leaves of Eucalyptus globulus against Escherichia coli and Staphylococcus aureus. Asian Pac J. Trop. Biomed. 2:739-42.
Rao, B.R., Kaul, P. N., Syamasundar, K.V., Ramesh, S. (2005). Chemical profiles of primary and secondary essential oils of palmarosa (Cymbopogon martinii (Roxb.) Wats var. motia Burk.), Ind. Crops Products, 21: 121-127,
Reich, S., Guilligay, D., Pflug, A., Malet, H., Berger, I., Crepin, T., Hart, D., Lunardi, T., Nanao, M., Ruigrok, R.W.H. (2014) Structural insight into cap-snatching and RNA synthesis by influenza polymerase. Nature. 516:361–366.
Ren, Y., Long, S., Cao, S. (2021) Molecular Docking and Virtual Screening of an Influenza Virus Inhibitor That Disrupts Protein-Protein Interactions. Viruses. 5;13(11):2229
Sebei, K., Sakouhi, F., Herchi, W., Khouja, M.L., Boukhchina,S.( 2015) Chemical composition and antibacterial activities of seven Eucalyptus species essential oils leaves. Biol. Res. 48:7.
Soorya, C., Balamurugan ,S., Basha, A.N., Kandeepan, C., Ramya, S., Jayakumararaj, R. (2021). Profile of Bioactive Phytocompounds in Essential Oil of Cymbopogon martinii from Palani Hills, Western Ghats, INDIA, J. Drug Delivery Therapeutics 11:60-65
Srimai, V., Ramesh, M., Parameshwar, K.S., Parthasarathy, T. (2013) Computer-aided design of selective Cytochrome P450 inhibitors and docking studies of alkyl resorcinol derivatives. Med. Chem. Res. 22: 5314-5323
Venkataraman, S., Prasad, B.V.L.S., Selvarajan,R. (2018). RNA Dependent RNA Polymerases: Insights from Structure, Function and Evolution. Viruses. 10;10(2):76.
Wu, C., Liu, Y., Yang, Y., Zhang, P., Zhong, W., Wang, Y., Wang, Q. (2020). Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharmaceutica Sinica B, 10: 766-788.
York, A., Fodor, E. (2013) Biogenesis, assembly, and export of viral messenger ribonucleoproteins in the influenza A virus infected cell. RNA Biol. 2013;10:1274–1282
Zeng, S., Kapur, A., Patankar, M.S., Xiong, M.P. (2015). Formulation, characterization, and antitumor properties of trans- and cis-citral in the 4T1 breast cancer xenograft mouse model. Pharm. Res. 32, (8) 2548–2558
DOI: https://doi.org/10.14421/biomedich.2023.122.515-524
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