Generic placeholder image

Infectious Disorders - Drug Targets

Author(s): Pugazhenthan Thangaraju*, Gopinathan Narasimhan, Vijayakumar Arumugam Ramamurthy, Meenalochini Prakash Gurunthalingam, Sree Sudha Tanguturi Yella, Sajitha Venkatesan and Eswaran thangaraju

DOI: 10.2174/1871526522666220718101544

DownloadDownload PDF Flyer Cite As
Molecular Docking Analysis of Adhatoda vasica with Thromboxane A2 Receptor (TXA2R) (6IIU) and Antiviral Molecules for Possible Dengue Complications

Article ID: e180722206836 Pages: 11

  • * (Excluding Mailing and Handling)

Abstract

Objective: The present study is an in silico model of platelet amplification potential of Adhatoda vasica, which can be used to treat thrombocytopenia in dengue complications.

Methods: Docking studies have proved to be an essential tool that facilitates the structural diversity of natural products to be harnessed in an organized manner. In the present study, vasicine containing natural anti-dengue potential was subjected to docking studies using Schrodinger glides software (ver.11.1). The docking study was carried out to find out the potential molecular targets for selected protein. The docking was carried out on different ligands, like vasicine, ramatroban, chloroquine, celgosivir, and standard eltrombopag downloaded from PubChem and retrieved to glide software and ligands prepared using lig prep wizard. Docking was performed using the ligand docking wizard of Glide-maestro 2018.

Results: The docking score of vasicine (-5.27) is nearly identical to the standard eltrombopag (-6.08), and both ligands bind with one hydrogen bond. The validation score of ramatroban is -12.39, binding with five hydrogen bonds, Celgosivir exhibited a docking score of -7.3 with three hydrogen bonds, and chloroquine displayed no hydrogen bond but had a docking score of -4.6.

Conclusion: Vasicine was found to be the most suitable target of platelet amplification potential from Adhatoda vasica. However, the molecular docking results are preliminary, and it has been indicated that vasicine could be one of the potential ligands to treat the thrombocytopenia of dengue; experimental evaluation will be carried out in the near future.

Keywords: Molecular docking, Adhatoda vasica, dengue, vasicine, celgosivir, chloroquine, antiviral property, molecules, platelet augmentation, eltrombopag, ramatroban, 6IIU.

Graphical Abstract

[1]
Gubler DJ. Dengue. In: Epidemiology of arthropod-borne viral diseases. Boca Raton: CRC Press, Inc. 1988; pp. 223-60.
[2]
Westaway EG, Blok J. Taxonomy and evolutionary relationships of flaviviruses. In: Dengue and dengue hemorrhagic fever. London, United Kingdom: CAB International 1997; pp. 147-73.
[3]
Anonymous . Dengue hemorrhagic fever, diagnosis, treatment and control. Geneva, Switzerland: World Health Organization 1986.
[4]
Sabin AB. Research on dengue during World War II. Am J Trop Med Hyg 1952; 1(1): 30-50.
[http://dx.doi.org/10.4269/ajtmh.1952.1.30] [PMID: 14903434]
[5]
Siler JF, Hall MW, Hitchens A. Dengue, its history, epidemiology, mechanism of transmission, etiology, clinical manifestations, immunity and prevention. Philipp J Sci 1926; 29: 1-304.
[6]
Kapoor M, Zhang L, Mohan PM, Padmanabhan R. Synthesis and characterization of an infectious dengue virus type-2 RNA genome (New Guinea C strain). Gene 1995; 162(2): 175-80.
[http://dx.doi.org/10.1016/0378-1119(95)00332-Z] [PMID: 7557426]
[7]
Waterman SH, Gubler DJ. Dengue fever. Clin Dermatol 1989; 7(1): 117-22.
[http://dx.doi.org/10.1016/0738-081X(89)90034-5] [PMID: 2647259]
[8]
Innis BL. Dengue and dengue hemorrhagic fever. Exo Viral Infect 1995; 103-46.
[9]
Available from: https://www.who.int/csr/resources/publications/dengue/024-33.pdf?ua=1
[10]
Subenthiran S, Choon TC, Cheong KC, et al. Carica papaya leaves juice significantly accelerates the rate of increase in platelet count among patients with dengue fever and dengue haemorrhagic fever. Evidence-Based Compl Alter Med 2013; 2013.
[http://dx.doi.org/10.1155/2013/616737]
[11]
Atal CK. Chemistry and pharmacology of vasicine —a new oxytocic and abortifacient Jammu-Tawi. Regional Research Laboratory 1980.
[12]
Gupta OP, Anand KK, Ghatak BJR, Atal CK. Vasicine, alkaloid of Adhatoda vasica, a promising uterotonic abortifacient. Indian J Exp Biol 1978; 16(10): 1075-7.
[PMID: 750386]
[13]
Grange JM, Snell NJC. Activity of bromhexine and ambroxol, semi-synthetic derivatives of vasicine from the Indian shrub Adhatoda vasica, against Mycobacterium tuberculosis in vitro. J Ethnopharmacol 1996; 50(1): 49-53.
[http://dx.doi.org/10.1016/0378-8741(95)01331-8] [PMID: 8778507]
[14]
Karthikeyan A, Shanthi V, Nagasathaya A. Preliminary phytochemical and antibacterial screening of crude extract of the leaf of Adhatoda vasica L. Int J Green Pharm 2009; 3(1): 78-80.
[http://dx.doi.org/10.4103/0973-8258.49381]
[15]
Shrivastava N, Srivastava A, Banerjee A, Nivsarkar M. Anti-ulcer activity of Adhatoda vasica Nees. J Herb Pharmacother 2006; 6(2): 43-9.
[http://dx.doi.org/10.1080/J157v06n02_04] [PMID: 17182484]
[16]
Ahmad B, Ali N, Bashir S, Choudhary MI, Azam A, Khan I. Parasiticidal, antifungal and antibacterial activities of Onosmagriffithii Vatke. Afr J Biotechnol 2009; 8(19): 5084-7.
[17]
Verma H, Patil PR, Kolhapure RM, Gopalkrishna V. Antiviral activity of the Indian medicinal plant extract Swertia chirata against herpes simplex viruses: A study by in-vitro and molecular approach. Indian J Med Microbiol 2008; 26(4): 322-6.
[http://dx.doi.org/10.1016/S0255-0857(21)01807-7] [PMID: 18974483]
[18]
Al-Shaibani IRM, Phulan MS, Arijo A, et al. Ovicidal and larvicidal properties of Adhatoda vasica (L.) extracts against gastrointestinal nematodes of sheep in vitro. Pak Vet J 2008; 28: 79-83.
[19]
Zama MMS, Singh HP, Kumar A. Comparative studies on Adathoda vasica and pancreatic tissue extract on wound healings in buffaloes. Indian Vet J 1991; 68: 864-6.
[20]
Atal CK, Sharma ML, Khajuria A, Kaul A, Arya RK. Thrombopoietic activity of vasicine hydrochloride. Indian J Exp Biol 1982; 20(9): 704-9.
[PMID: 7160870]
[21]
Gangwar.A. Ghosh KA. Medicinal uses and Pharmacological activity of Adhatoda Vasica. Int J Herb Med 2014; 2(1): 88-91.
[22]
Jain MP, Sharma VK. Phytochemical investigation of roots of Adhatoda vasica. Planta Med 1982; 46(4): 250.
[http://dx.doi.org/10.1055/s-2007-971226] [PMID: 17396985]
[23]
Chavan R. Anti-viral activity of Indian medicinal plant Justicia adhatoda against Herpes Simplex virus:An in-vitro study. Int J Pharm Bio Sci 2013; 4(4): 769-78.
[24]
Chavan R, Choudhary A. Article 2014; (43): 231-6.
[25]
Warfield KL, Plummer EM, Sayce AC, et al. Inhibition of endoplasmic reticulum glucosidases is required for in vitro and in vivo dengue antiviral activity by the iminosugar UV-4. Antiviral Res 2016; 129: 93-8.
[http://dx.doi.org/10.1016/j.antiviral.2016.03.001] [PMID: 26946111]
[26]
ClinicalTrialsgov Available from: https://clinicaltrials.gov/ct2/home
[27]
Low JG, Sung C, Wijaya L, et al. Efficacy and safety of celgosivir in patients with dengue fever (CELADEN): a phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial. Lancet Infect Dis 2014; 14(8): 706-15.
[http://dx.doi.org/10.1016/S1473-3099(14)70730-3] [PMID: 24877997]
[28]
Chen YL, Abdul Ghafar N, Karuna R, et al. Activation of peripheral blood mononuclear cells by dengue virus infection depotentiates balapiravir. J Virol 2014; 88(3): 1740-7.
[http://dx.doi.org/10.1128/JVI.02841-13] [PMID: 24257621]
[29]
Bhatt S, Gething PW, Brady OJ, et al. The global distribution and burden of dengue. Nature 2013; 496(7446): 504-7.
[http://dx.doi.org/10.1038/nature12060] [PMID: 23563266]
[30]
WHO Dengue and severe dengue. Available from: http://www.who.int/mediacentre/factsheets/fs117/en/
[31]
Ngo NT, Cao XT, Kneen R, et al. Acute management of dengue shock syndrome: a randomized double-blind comparison of 4 intravenous fluid regimens in the first hour. Clin Infect Dis 2001; 32(2): 204-13.
[http://dx.doi.org/10.1086/318479] [PMID: 11170909]
[32]
Hung NT. Fluid management for dengue in children. Paediatr Int Child Health 2012; 32(Suppl 1 (s1)): 39-42.
[http://dx.doi.org/10.1179/2046904712Z.00000000051]
[33]
Lanciotti RS, Calisher CH, Gubler DJ, Chang GJ, Vorndam AV. Rapid detection and typing of dengue viruses from clinical samples by using reverse transcriptase-polymerase chain reaction. J Clin Microbiol 1992; 30(3): 545-51.
[http://dx.doi.org/10.1128/jcm.30.3.545-551.1992] [PMID: 1372617]
[34]
Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today’s diseases? Lancet Infect Dis 2003; 3(11): 722-7.
[http://dx.doi.org/10.1016/S1473-3099(03)00806-5] [PMID: 14592603]
[35]
Savarino A, Di Trani L, Donatelli I, Cauda R, Cassone A. New insights into the antiviral effects of chloroquine. Lancet Infect Dis 2006; 6(2): 67-9.
[http://dx.doi.org/10.1016/S1473-3099(06)70361-9] [PMID: 16439323]
[36]
Vincent MJ, Bergeron E, Benjannet S, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2005; 2(1): 69.
[http://dx.doi.org/10.1186/1743-422X-2-69] [PMID: 16115318]
[37]
Adachi K, Ichinose T, Takizawa N, Watanabe K, Kitazato K, Kobayashi N. Inhibition of betanodavirus infection by inhibitors of endosomal acidification. Arch Virol 2007; 152(12): 2217-24.
[http://dx.doi.org/10.1007/s00705-007-1061-7] [PMID: 17891330]
[38]
Di Trani L, Savarino A, Campitelli L, et al. Different pH requirements are associated with divergent inhibitory effects of chloroquine on human and avian influenza A viruses. Virol J 2007; 4(1): 39.
[http://dx.doi.org/10.1186/1743-422X-4-39] [PMID: 17477867]
[39]
Keyaerts E, Li S, Vijgen L, et al. Antiviral activity of chloroquine against human coronavirus OC43 infection in newborn mice. Antimicrob Agents Chemother 2009; 53(8): 3416-21.
[http://dx.doi.org/10.1128/AAC.01509-08] [PMID: 19506054]
[40]
Martinson JA, Montoya CJ, Usuga X, Ronquillo R, Landay AL, Desai SN. Chloroquine modulates HIV-1-induced plasmacytoid dendritic cell alpha interferon: implication for T-cell activation. Antimicrob Agents Chemother 2010; 54(2): 871-81.
[http://dx.doi.org/10.1128/AAC.01246-09] [PMID: 19949061]
[41]
Savarino A, Lucia MB, Rastrelli E, et al. Anti-HIV effects of chloroquine: inhibition of viral particle glycosylation and synergism with protease inhibitors. J Acquir Immune Defic Syndr 2004; 35(3): 223-32.
[http://dx.doi.org/10.1097/00126334-200403010-00002] [PMID: 15076236]
[42]
Rolain JM, Colson P, Raoult D. Recycling of chloroquine and its hydroxyl analogue to face bacterial, fungal and viral infections in the 21st century. Int J Antimicrob Agents 2007; 30(4): 297-308.
[http://dx.doi.org/10.1016/j.ijantimicag.2007.05.015] [PMID: 17629679]
[43]
Lindenbach BD, Rice CM. Molecular biology of flaviviruses. Adv Virus Res 2003; 59: 23-61.
[http://dx.doi.org/10.1016/S0065-3527(03)59002-9] [PMID: 14696326]
[44]
Hober D, Poli L, Roblin B, et al. Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta) in dengue-infected patients. Am J Trop Med Hyg 1993; 48(3): 324-31.
[http://dx.doi.org/10.4269/ajtmh.1993.48.324] [PMID: 8470771]
[45]
Pinto LMO, Oliveira SA, Braga ELA, Nogueira RMR, Kubelka CF. Increased pro-inflammatory cytokines (TNF-alpha and IL-6) and anti-inflammatory compounds (sTNFRp55 and sTNFRp75) in Brazilian patients during exanthematic dengue fever. Mem Inst Oswaldo Cruz 1999; 94(3): 387-94.
[http://dx.doi.org/10.1590/S0074-02761999000300019] [PMID: 10348988]
[46]
Gandini M, Reis SRNI, Torrentes-Carvalho A, et al. Dengue-2 and yellow fever 17DD viruses infect human dendritic cells, resulting in an induction of activation markers, cytokines and chemokines and secretion of different TNF-α and IFN-α profiles. Mem Inst Oswaldo Cruz 2011; 106(5): 594-605.
[http://dx.doi.org/10.1590/S0074-02762011000500012] [PMID: 21894381]
[47]
Molyneux RJ, Roitman JN, Dunnheim G, Szumilo T, Elbein AD. 6-Epicastanospermine, a novel indolizidine alkaloid that inhibits alpha-glucosidase. Arch Biochem Biophys 1986; 251(2): 450-7.
[http://dx.doi.org/10.1016/0003-9861(86)90351-6] [PMID: 3099643]
[48]
Taylor DL, Sunkara PS, Liu PS, Kang MS, Bowlin TL, Tyms AS. 6-0-butanoylcastanospermine (MDL 28,574) inhibits glycoprotein processing and the growth of HIVs. AIDS 1991; 5(6): 693-8.
[http://dx.doi.org/10.1097/00002030-199106000-00008] [PMID: 1652979]
[49]
Kaita K, Yoshida E, Kunimoto D, Anderson F, Sherman M, Marotta P, et al. Phase II proof of concept study of celgosivir in combination with peginterferon alfa-2b and ribavirin in chronic hepatitis C genotype-1 non-responder patients Digestive Disease Weekly May. Abstr 2007; p. 442.
[50]
Cáceres DD, Hancke JL, Burgos RA, Wikman GK. Prevention of common colds with Andrographis paniculata dried extract. A Pilot double blind trial. Phytomedicine 1997; 4(2): 101-4.
[http://dx.doi.org/10.1016/S0944-7113(97)80051-7] [PMID: 23195395]
[51]
Leon IC. Tang, Anna PK Ling, Rhun Y Koh, Soi M Chye and Kenny GL Voon. Screening of anti-dengue activity in methanolic extracts of medicinal plants. BMC Complement Altern Med 2012; 12(1): 3.
[http://dx.doi.org/10.1186/1472-6882-12-3]
[52]
Hossain MT, Hoq MO. Therapeutic use of Adhatoda vasica. Asian J Med Biol Res 2016; 2(2): 156-63.
[http://dx.doi.org/10.3329/ajmbr.v2i2.29005]
[53]
Salalamp P, Temsiririrkkul R, Chuakul W, et al. Medicinal Plants in Siri Ruckhachati Garden. Bangkok: Amarin Printing Group Co. 1992; p. 37.
[54]
Dymock W, Waeden CJH, Hooper D. Pharmacographia Indica, A History of the Principal Drugs of Vegetable Origin Paul, Trech. London: Trubner& Co. Ltd 1890; pp. 50-4.
[55]
Kalai AR, Jeeva GR, Elangovan S, et al. A combination of nilavembu kudineer and adathoda imanapagu in the management of dengue fever. Int J Curr Res 2013; 5(4): 978-81.