Molecular Docking Studies of Selected Medicinal Drugs as Dengue Virus-2 Protease Inhibitors

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 (-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; perencat; Denggi adalah sejenis penyakit yang boleh membawa maut dan sehingga kini tiada sebarang ubat untuk merawat penyakit tersebut. Mengedok molekul secara in 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

A Computational Approach on Understanding Structural Interactions of Envelope Protein of Dengue Virus Bound With Squalene, a Prototype Anti-Viral Compound

“…Ariza et al [16] showed that molecular dockings between curcumin and RdRp domain of the NS5 protein, also a key element in the viral replication, with a binding energy of-6.2 Kcal/mol. Rufaidah Othman et al [17] demonstrated the binding interactions of antibiotics pinostrobin (with binding energy of-5.33 Kcal/mol), doxycycline (with binding energy of-5.15 Kcal/mol), 4-hydroxypanduratin A (with binding energy of-4.45 Kcal/mol), meclofenamic acid (with binding energy of-3.64 Kcal/mol) androlitetracycline (with binding energy of-3.21 Kcal/mol) against NS2B-NS3 proteases of dengue viruses. Nasution Aini and Tambunan [18] listed out 18 promising leads to chemotherapy treatments of the dengue diseases based on the comprehensive analyses of molecular docking complexes of 308 diverse molecules bound with NS2B-NS3 proteases of the dengue viruses.…”

Anti-inflammatory Activity of Polyphenols from Labisia pumila Leaves Extract

“…The grid box parameters employed for all target proteins were listed in Table 2 which were inspired by Rabiu et al [20] and Mechqoq et al [21] with some modifications. The Lamarckian genetic algorithm was employed and the parameters were defined according to the Othman et al [22]. The docking process was conducted by utilizing Autodock 4.2.6.…”

Finding Lead Compounds for Dengue Antivirals from a Collection of Old Drugs through In Silico Target Prediction and Subsequent In Vitro Validation

“…In the docking exercise, all drugs and the two newly developed compounds were found to bind to the binding pocket at the right side of the active site region (S1 pocket), as observed in Figure 6. Interestingly, this site is much broader and more shallow than the binding pocket at the left region (S2 pocket), 20 yet, most of the interactions were observed to be at this site. It was identified that the S1 region has much more hydrophobic residues compared to the S2 region.…”