Molecular Docking and Molecular Dynamic Simulation of 1,5-Benzothiazepine Chalcone Derivative Compounds as Potential Inhibitors for Zika Virus Helicase


  • Neni Frimayanti Sekolah Tinggi Ilmu Farmasi Riau, Pekanbaru, Riau, Indonesia, Indonesia
  • Musyirna Rahmah Nasution Sekolah Tinggi Ilmu Farmasi Riau, Pekanbaru, Riau, Indonesia, Indonesia
  • Elsa Etavianti Sekolah Tinggi Ilmu Farmasi Riau, Pekanbaru, Riau, Indonesia, Indonesia



Docking, MD simulation, 1, 5-benzothiazepine, Zika virus, Suramin


Zika virus caused of the emerging infections characterized by fever, Guillain-Barré syndrome (GBS) for adults. In the current work, we aimed to study the binding orientation of 1,5-benzothiazepine compounds as new potential agent against Zika virus inhibitor through molecular docking and molecular dynamic simulation. Since, 1-5-Benzothiazepines are particular interest for drug discovery and they also has some biological activities. However, their antiviral activities and in silico studies of the binding to their biological targets have not been extensively investigated. Molecular docking study of 1,5-benzothiazepine chalcone derivatives compounds with protein target 5GJB (PDB ID) and this protein was taken from the crystallographic structure. In this study, twelve 1,5-benzothiazepine chalcone derivative compounds were docked to the protein with the grid box along x, y and z radius of 26.85, 28.17 and 24.43 Å, respectively. Suramin was used as positive control. Thus, it can be used as a reference for design new inhibitors for Zika virus helicase. Based on the docking results, it is observed that compounds MA3 and MA8 are estimated to have activity as inhibitors for Zika virus helicase with binding free energy values of -4.6490 and -4.9291 kcal/mol, respectively. MA3 and MA8 were also stable during the MD simulations with the hydrogen bonding are still maintained before and after MD simulation. Furthermore, both of these compounds can be used an early stage for drug design and drug delivery process.


Newman, C., Friedrich, T. C. & O’Connor, D. H., Macaque monkeys in Zika virus research: 1947–present. Curr. Opin. Virol., 25: 34–40 (2017).

Hamel, R., Dejarnac, O., Wichit, S., Ekchariyawat, P., Neyret, A., Luplertlop, N., Perera-Lecoin, M., et al., Biology of Zika Virus Infection in Human Skin Cells. J. Virol., 89(17): 8880–8896 (2015).

Tan, C. W., Sam, I. C., Chong, W. L., Lee, V. S. & Chan, Y. F., Polysulfonate suramin inhibits Zika virus infection. Antiviral Res., 143(9): 186–194 (2017).

Quanquin, N., Wang, L. & Cheng, G., Potential for treatment and a Zika virus vaccine. Curr. Opin. Pediatr., 29(1): 114–121 (2017).

Vyawahare, D., Ghodke, M. & Nikalje, A. P., Green synthesis and pharmacological screening of novel 1,5-Benzothiazepines as CNS agents. Int. J. Pharm. Pharm. Sci., 2(2): 27–29 (2010).

Bajod, S. S., Synthesis and biological screening of some heterocycles derived from piperonal. Acta Chim. Pharm. Indica, 3(4): 261–267 (2013).

Mor, S., Pahal, P. & Narasimhan, B., Synthesis, characterization, biological evaluation and QSAR studies of 11-p-substituted phenyl-12-phenyl-11a,12-dihydro-11H-indeno[2,1-c][1,5] benzothiazepines as potential antimicrobial agents. Eur. J. Med. Chem., 57: 196–210 (2012).

Gaikwad, S., Suryawanshi, V. S. & Lohar, K., Synthesis and antimicrobial study of novel 2, 3-diydro-4-(naphtho [2, 1-b] furan-2yl)-2-substitued [1, 5] benzothiazepines. J. Chem. Biol. Phys. Sci., 33(22): 936–940 (2013).

Garg, N., Chandra, T., Archana., Jain, A. B. & Kumar, A., Synthesis and evaluation of some new substituted benzothiazepine and benzoxazepine derivatives as anticonvulsant agents. Eur. J. Med. Chem., 45(4): 1529–1535 (2010).

Dong, C. K., Urgaonkar, S., Cortese, J. F., Gamo, F.-J., Garcia-Bustos, J. F., Lafuente, M. J., Patel, V., et al., Identification and Validation of Tetracyclic Benzothiazepines as Plasmodium falciparum Cytochrome bc1 Inhibitors. Chem. Biol., 18(12): 1602–1610 (2011).

Di Santo, R. & Costi, R., 2H-Pyrrolo[3,4-b] [1,5]benzothiazepine derivatives as potential inhibitors of HIV-1 reverse transcriptase. Farmaco, 60(5): 385–392 (2005).

Ameta, K. L., Rathore, N. S. & Kumar, B., Synthesis and preliminary evaluation of novel 1, 5-benzothiazepine derivatives as anti-lung cancer agents. Int. J. Pharm., 3(2): 328–333 (2013).

Badshah, S. L., Ahmad, N., Ur Rehman, A., Khan, K., Ullah, A., Alsayari, A., Muhsinah, A. Bin., et al., Molecular docking and simulation of Zika virus NS3 helicase. BMC Chem., 13(1): 67 (2019).

Ferreira, L., dos Santos, R., Oliva, G. & Andricopulo, A., Molecular Docking and Structure-Based Drug Design Strategies. Molecules, 20(7): 13384–13421 (2015).

Yaeghoobi, M., Synthesis of chalcone-based six and seven membered heterocyclic compounds and their biological activities against H1N1 virus. University of Malaya, (2012).

Tian, H., Ji, X., Yang, X., Zhang, Z., Lu, Z., Yang, K., Chen, C., et al., Structural basis of Zika virus helicase in recognizing its substrates. Protein Cell, 7(8): 562–570 (2016).

Eryanti, Y., Zamri, A., Frimayanti, N., Teruna, H. Y., Supratmman, U., Herlina, T. & Shiono, Y., Synthesis, Structure-Activity Relationship, Docking and Molecular Dynamic Simulation of Curcumin Analogues Against HL-60 for Anti Cancer Agents (Leukemia). Orient. J. Chem., 33(5): 2164–2172 (2017).

Purnomo, H., Kimia Komputasi Untuk Farmasi dan Ilmu Terkait. Pustaka pelajar, (2013).

Levita, J. & Mustarichie, R., Pemodelan Molekul Dalam Kimia Medisinal. Graha Ilmu, (2012).

Syahputra, G., Ambarsari, L. & Sumaryada, T., Simulasi docking kurkumin enol, bisdemetoksikurkumin dan analognya sebagai inhibitor enzim12-lipoksigenase. J. Biofisika, 10(1): 55–67 (2014).

Meiyanto, E., Docking kurkumin dan senyawa analognya pada reseptor progesteron: studi interaksinya sebagai selective progesterone receptor modulators (SPRMs). Pharmacon J. Farm. Indones., 13(2): 55–60 (2012).

Siswandono. & Soekarjo., Kimia Medisinal Jilid II. Airlangga Univeristy Press, (2006).

Finch, C. A., Industrial water soluble polymers. Royal Society of Chemistry, (1996).

Schaefer, T., Wildman, T. A., Sebastian, R. & McKinnon, D. M., The phenyl group as a hydrogen bond acceptor in 2-phenylphenol derivatives. Substituent comparisons. Can. J. Chem., 62(12): 2692–2696 (1984).

Suhud, F., Siswandono, S. & Budiati, T., Sintesis dan Uji Aktivitas Senyawa 1-Benzil-3-benzoilurea Tersubstitusi Bromo, Kloro, Floro dan Triflorometil pada posisi para sebagai Agen Antiproliferatif. Media Pharm. Indones., 1(3): 154–163 (2017).

Neni, F., Marzieh, Y., Hamid, N., Ihsan, I. & Meysam, A., In silico studies and biological evaluation of chalcone-based 1,5-benzothiazepines as new potential H1N1 neuraminidase inhibitors. J. Appl. Pharm. Sci., 10(10): 086–094 (2020).




How to Cite

Frimayanti, N., Nasution, M. R., & Etavianti, E. (2021). Molecular Docking and Molecular Dynamic Simulation of 1,5-Benzothiazepine Chalcone Derivative Compounds as Potential Inhibitors for Zika Virus Helicase. Jurnal Riset Kimia, 12(1), 44–52.




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