GAS CHROMATOGRAPHY MASS SPECTROMETRY (GC-MS) ANALYSIS AND DOCKING STUDIES OF ANDROGRAPHIS PANICULATA AGAINST DENGUE FEVER
Objective: To evaluate gas chromatography- mass spectrometry (GC-MS) analysis and molecular docking studies of ethanol extract of Andrographis paniculata (Burm.f.) against type 2 dengue virus (DEN2).
Methods: The ethanol extract of A. paniculata compounds were identified by GC-MS analysis. These compounds were further analysed for their activities against NS2B/NS3 protease of DEN2 by molecular docking studies.
Results: The nine compounds obtained from the ethanol extract of A. paniculata were characterized and docked. Among these nine compounds, Vor-diazepam,3-[[N-hydroxymethyl]aminocarbonyloxy], Dasycarpidan-1-methanol, acetate (ester), Ethanol, 2-(9, 12-octadecadienyloxy)-, (Z, Z), Gibb-2-ene-1,10-dicarboxylicacid4a,7-dihydroxy-1-methylene-1,4a-lactone,10 methylester, (1a,4aa,4ba,10a) were found to show better interaction energetically and also showed crucial interactions with the active site of NS2B/NS3 protease. Thus A. paniculata is suggested to be a medicinally important plant to cure dengue fever.
Conclusions: From the result, it can be concluded that the crude extract of A. paniculata compounds positively inhibit the activities of NS2B/NSB protease of DEN2 thus by preventing the dengue viral infection. This strategy reflects a logical progression for an early stage drug discovery which can be used to identify new drug candidates.Â
Kautner I., Robinson, M.J. and Kuhnle U. Dengue virus infection: epidemiology, pathogenesis, clinical presentation, diagnosis, and prevention. The Journal of pediatrics. 1997; 131(4):516-524.
Yin Z, Patel SJ, Wang WL, Wang G, Chan WL, Rao KR, Alam J, Jeyaraj DA, Ngew X, Patel V, Beer D. Peptide inhibitors of Dengue virus NS3 protease. Part 1: Warhead. Bioorganic & medicinal chemistry letters. 2006; 16(1):36-9.
Bressanelli S, Stiasny K, Allison SL, Stura EA, Duquerroy S, Lescar J, Heinz FX, Rey FA. Structure of a flavivirus envelope glycoprotein in its lowâ€pHâ€induced membrane fusion conformation. The EMBO journal. 2004; 23(4):728-38.
Irie K, Mohan PM, Sasaguri Y, Putnak R, Padmanabhan R. Sequence analysis of cloned dengue virus type 2 genome (New Guinea-C strain). Gene. 1989; 75(2):197-211.
Falgout B, Pethel M, Zhang YM, Lai CJ. Both nonstructural proteins NS2B and NS3 are required for the proteolytic processing of dengue virus nonstructural proteins. Journal of virology. 1991; 65(5):2467-75.
Yusof R, Clum S, Wetzel M, Murthy HK, Padmanabhan R. Purified NS2B/NS3 serine protease of dengue virus type 2 exhibits cofactor NS2B dependence for cleavage of substrates with dibasic amino acids in vitro. Journal of Biological Chemistry. 2000; 275(14):9963-9.
Gorbalenya AE, Donchenko AP, Koonin EV, Blinov VM. N-terminal domains of putative helicases of flavi-and pestiviruses may be serine proteases. Nucleic acids research. 1989; 17(10):3889-97.
Lescar J, Luo D, Xu T, Sampath A, Lim SP, Canard B, Vasudevan SG. Towards the design of antiviral inhibitors against flaviviruses: the case for the multifunctional NS3 protein from Dengue virus as a target. Antiviral research. 2008; 80(2):94-101.
Brinkworth RI, Fairlie DP, Leung D, Young PR. Homology model of the dengue 2 virus NS3 protease: putative interactions with both substrate and NS2B cofactor. Journal of General Virology. 1999; 80(5):1167-77.
Arias CF, Preugschat F, Strauss JH. Dengue 2 virus NS2B and NS3 form a stable complex that can cleave NS3 within the helicase domain. Virology. 1993; 193(2):888-99.
Clum S, Ebner KE, Padmanabhan R. Cotranslational membrane insertion of the serine proteinase precursor NS2B-NS3 (Pro) of dengue virus type 2 is required for efficient in vitro processing and is mediated through the hydrophobic regions of NS2B. Journal of Biological Chemistry. 1997; 272(49):30715-23.
Othman R, Wahab HA, Yusof R, Rahman NA. Analysis of secondary structure predictions of dengue virus type 2 NS2B/NS3 against crystal structure to evaluate the predictive power of the in silico methods. In silico biology. 2007; 7(2):215-24.
Leyssen P, De Clercq E, Neyts J. Perspectives for the Treatment of Infections withFlaviviridae. Clinical microbiology reviews. 2000; 13(1):67-82.
Sampath A, Padmanabhan R. Molecular targets for flavivirus drug discovery. Antiviral research. 2009; 81(1):6-15.
Govindarajan M. Evaluation of Andrographis paniculata Burm. f.(Family: Acanthaceae) extracts against Culex quinquefasciatus (Say.) and Aedes aegypti (Linn.)(Diptera: Culicidae). Asian Pacific Journal of Tropical Medicine. 2011; 4(3):176-81.
Gabrielian ES, Shukarian AK, Goukasova GI, Chandanian GL, Panossian AG, Wikman G, Wagner H. A double blind, placebo-controlled study of Andrographis paniculata fixed combination Kan Jang in the treatment of acute upper respiratory tract infections including sinusitis. Phytomedicine. 2002; 9(7):589-97.
Sule A, Ahmed QU, Saman OA, Omar MN. Bacteriostatic and bactericidal activity of the polar and non-polar extracts of Andrographis paniculata against skin disease causing pathogenic bacteria. J Med Plant Res. 2011; 5:7-14.
Wiart C, Kumar K, Yusof MY, Hamimah H, Fauzi ZM, Sulaiman M. Antiviral properties of entâ€labdene diterpenes of Andrographis paniculata nees, inhibitors of herpes simplex virus type 1. Phytotherapy Research. 2005; 19(12):1069-70.
Chao WW, Kuo YH, Lin BF. Anti-inflammatory activity of new compounds from Andrographis paniculata by NF-ÎºB transactivation inhibition. Journal of agricultural and food chemistry. 2010; 58(4):2505-12.
Calabrese C, Berman SH, Babish JG, Ma X, Shinto L, Dorr M, Wells K, Wenner CA, Standish LJ. A phase I trial of andrographolide in HIV positive patients and normal volunteers. Phytotherapy Research. 2000; 14(5):333-8.
Li HB, Wong CC, Cheng KW, Chen F. Antioxidant properties in vitro and total phenolic contents in methanol extracts from medicinal plants. LWT-Food Science and Technology. 2008; 41(3):385-90.
Iruretagoyena MI, Tobar JA, GonzÃ¡lez PA, SepÃºlveda SE, Figueroa CA, Burgos RA, Hancke JL, Kalergis AM. Andrographolide interferes with T cell activation and reduces experimental autoimmune encephalomyelitis in the mouse. Journal of Pharmacology and Experimental Therapeutics. 2005; 312(1):366-72.
Rajani M, Shrivastava N and Ravishankara MN. A rapid method for isolation of Andrographolide from Andrographispaniculatanees (kalmegh). Pharmaceutical Biology. 2000; 38(3): 204-9.
Roy S, Rao K, Bhuvaneswari CH, Giri A, Mangamoori LN. Phytochemical analysis of Andrographis paniculata extract and its antimicrobial activity. World Journal of Microbiology and Biotechnology. 2010; 26(1):85.
Jones WP, Kinghorn AD. Extraction of plant secondary metabolites. In: Satyajit D. Sarker, Zahid Latif, Alexander I. Gray, editors. Natural products isolation. 2nd edition. U.S: Humana press; 2005:323-51.
Devi OZ, Rao KS, Bidalia A, Wangkheirakpam R, Singh OM. GC-MS Analysis of Phytocomponents and Antifungal Activities of Zanthoxylum acanthopodium DC. Collected from Manipur, India. European Journal of Medicinal Plants. 2015; 10(1):1-9.
Gnanavel V, Saral AM. GC-MS analysis of petroleum ether and ethanol leaf extracts from Abrus precatorius Linn. International Journal of Pharma and Bio Sciences. 2013; 4(3):37-44.
Thangavel M, Umavathi S, Thangam Y, Thamaraiselvi A, Ramamurthy M. GC-MS Analysis and Larvicidal Activity of Andrographis paniculata (Burm. F) Wall. Ex Nees. against the Dengue Vector Aedes aegypti (L)(Diptera: Culicidae). International Journal of Current Microbiology and Applied Sciences. 2015; 4(7):392-403.
Lee YK, Tan SK, Wahab HA, Rohana Y. Nonsubstrate based inhibitors of dengue virus serine protease: a molecular docking approach to study binding interactions between protease and inhibitors. Asia Pacific Journal of Molecular Biology & Biotechnology. 2007; 15(2):53-9.
Kalva S, Vadivelan S, Sanam R, Jagarlapudi SA, Saleena LM. Lead identification and optimization of novel collagenase inhibitors; pharmacophore and structure based studies. Bioinformation. 2012; 8(7):301.
Tomlinson SM, Watowich SJ. Anthracene-based inhibitors of dengue virus NS2Bâ€“NS3 protease. Antiviral research. 2011; 89(2):127-35.
Rajeswari G, Murugan M, Mohan VR. GC-MS analysis of bioactive components of Hugonia mystax L.(Linaceae). Research Journal of Pharmaceutical, Biological and Chemical Sciences. 2012; 3(4):301-8.
Santos CC, Salvadori MS, Mota VG, Costa LM, de Almeida AA, de Oliveira GA, Costa JP, de Sousa DP, de Freitas RM, de Almeida RN. Antinociceptive and antioxidant activities of phytol in vivo and in vitro models. Neuroscience journal. 2013.
Braestrup C, Squires RF. Specific benzodiazepine receptors in rat brain characterized by high-affinity (3H) diazepam binding. Proceedings of the National Academy of Sciences. 1977; 74(9):3805-9.
Karuppasamy Rajalakshmi, Veerabahu Ramasamy Mohan. MS Analysis of Bioactive Components of Myxopyrum serratulum A.W. Hill (Oleaceae). International Journal of Pharmaceutical Sciences Review and Research. 2016; 38(1): 30-35