Sains Malaysiana 46(10)(2017): 1865–1875
http://dx.doi.org/10.17576/jsm-2017-4610-25
Molecular Docking Studies of Selected Medicinal Drugs as Dengue
Virus-2 Protease Inhibitors
(Kajian Mengedok Molekul Dadah Ubatan Terpilih sebagai Perencat Protease Virus-2 Denggi)
RUFAIDAH OTHMAN1, ROZANA OTHMAN2, AIDA BAHARUDDIN3, NAGASUNDARA RAMANAN RAMAKRISHNAN4, NOORSAADAH ABD RAHMAN5, ROHANA YUSOF6,7 & SAIFUL ANUAR KARSANI1*
1Institute of
Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala
Lumpur, Federal Territory, Malaysia
2Department of
Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur,
Federal Territory, Malaysia
3Department of
Biotechnology, Faculty of Science, Lincoln University College, 47301 Petaling Jaya, Selangor Darul Ehsan, Malaysia
4School of Engineering,
Monash University Bandar Sunway, 46150 Bandar Sunway, Selangor Darul Ehsan, Malaysia
5Department of
Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur,
Federal Territory, Malaysia
6Department of
Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala
Lumpur, Federal Territory, Malaysia
7Drug Design and
Development Research Group (DDDRG), University of Malaya, 50603 Kuala Lumpur,
Federal Territory, Malaysia
Diserahkan: 28 Julai 2016/Diterima: 20 Mac 2017
ABSTRACT
Dengue is a
potentially deadly disease with no effective drug. An in silico molecular docking was performed using Autodock 4.2.6 to investigate the molecular interactions
between protease inhibitors, comprising antibiotic derivatives namely
doxycycline (3), rolitetracycline (5)
and a non-steroidal anti-inflammatory drug (NSAID), meclofenamic acid (4), against the NS2B-NS3
protease from dengue virus-2 (DENV-2). The non-competitive
inhibitor (3) showed lower binding energy (-5.15 kcal/mol) than the predicted competitive inhibitors 4 and 5 (-3.64 and -3.21 kcal/mol, respectively).
Structural analyses showed compound 3 that bound to a specific
allosteric site, interacted with Lys74, a significant amino acid residue bonded
to one of the catalytic triad, Asp75. Compounds 4 and 5 showed
direct binding with two of the catalytic triad, His51 and Ser135, hence,
predicted to be competitive inhibitors.
Keywords: Dengue
virus-2; docking; inhibitors; NS2B-NS3 protease
ABSTRAK
Denggi adalah sejenis penyakit yang boleh membawa maut dan sehingga kini tiada sebarang ubat untuk merawat penyakit tersebut. Mengedok molekul secarain silico menggunakan Autodock 4.2.6 telah dijalankan untuk mengkaji interaksi molekul antara perencat protease yang terdiri daripada derivatif antibiotik iaitu doxycycline (3) dan rolitetracycline (5) dan dadah anti-radang bukan steroid (NSAID), asid meklofenamik (4), terhadap NS2B-NS3 daripada virus denggi-2 (DENV-2). Perencat tidak-kompetitif (3) menunjukkan tenaga ikatan yang lebih rendah (-5.15 kcal/mol) berbanding sebatian 4 dan 5 (masing-masing -3.64 dan -3.21
kcal/mol). Analisis struktur menunjukkan sebatian 3 yang terikat pada kawasan alosterik, berinteraksi dengan Lys74, iaitu residu asid amino yang terikat dengan salah satu daripada residu triad pemangkinan,
Asp75. Sebatian 4 dan 5 pula menunjukkan ikatan langsung dengan dua triad pemangkinan iaitu His51 dan Ser135, justeru diramalkan sebagai perencat kompetitif.
Kata kunci: Mengedok;
NS2B-NS3 protease; perencat; virus denggi-2
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*Pengarang untuk surat-menyurat; email: saifule78@um.edu.my