Sains Malaysiana 49(3)(2020): 537-544

http://dx.doi.org/10.17576/jsm-2020-4903-08

Computational Quest for Finding Potential Ebola VP40 Inhibitors: A Molecular Docking Study

(Pencarian Pengiraan untuk Mencari Potensi Perencat Ebola VP40: Suatu Kajian Mengedok Molekul)

MOHAMAD ARIFF MOHAMAD YUSSOFF¹, AZZMER AZZAR ABD HAMID^1,3, SHAFIDA ABD HAMID² & KHAIRUL BARIYYAH ABD HALIM^1,3*

¹Department of Biotechnology, Kulliyyah of Science, International Islamic University Malaysia, 25200 Kuantan, Pahang Darul Makmur, Malaysia

²Department of Chemistry, Kulliyyah of Science, International Islamic University Malaysia, 25200 Kuantan, Pahang Darul Makmur, Malaysia

³Research Unit for Bioinformatics and Computational Biology, Kulliyyah of Science, International Islamic University Malaysia, 25200 Kuantan, Pahang Darul Makmur, Malaysia

Received: 1 August 2019/Accepted: 5 December 2019

ABSTRACT

Interaction of Ebola virus matrix protein VP40 with RNA is crucial in the early infection stage to facilitate the transcription of the viral gene. Thus, VP40 is a promising target to inhibit the Ebola virus from spreading. This study aims to identify and optimize ligands that can potentially block the VP40-RNA binding site. A total of 42 compounds from previously studied ligands from the literature were simulated against the RNA binding site using Autodock Vina. The top ten ligands were used as templates for similarity search in ZINC database followed by structured-based virtual screening. Then, the ADME properties of the top compounds were predicted computationally using SwissADME server. Our results showed that Q-96 (ZINC ID: 1338855) is the best docked compound with binding free energy of -7.5 kcal/mol. The compound also has satisfactory ADME properties prediction with good lipophilicity value, moderate water solubility and high gastrointestinal absorption. Besides, this ligand does not violate any drug likeness rules as well as no PAINS and Brenk alerts, indicate it has the properties as a drug. Thus, it is worth to carry out further investigations on this structure more in silico as well as in vitro and in vivo levels towards finding the treatment for Ebola virus disease. 

Keywords: ADME; Ebola virus; molecular docking: VP40 matrix protein

ABSTRAK

Interaksi matriks virus Ebola VP40 dengan RNA adalah penting dalam peringkat jangkitan awal untuk memudahkan transkripsi gen virus. Oleh itu, VP40 adalah sasaran yang sesuai bagi menghalang virus Ebola daripada terus merebak. Kajian ini bertujuan untuk mengenal pasti dan mengoptimumkan ligan yang berpotensi menghalang tapak pengikat VP40-RNA. Sejumlah 42 sebatian daripada kajian terdahulu telah disimulasi di tapak pengikat RNA menggunakan Autodock Vina. Sepuluh ligan terbaik telah dipilih sebagai templat pencarian persamaan dalam pangkalan data ZINC diikuti oleh penyaringan maya berasaskan struktur. Ciri-ciri ADME sebatian telah diramalkan secara komputasi menggunakan pelayan SwissADME. Keputusan kajian kami menunjukkan bahawa Q-96 (ZINC ID: 1338855) adalah sebatian terbaik dengan tenaga bebas pengikat -7.5 kcal/mol. Sebatian ini juga menunjukkan sifat ADME yang memuaskan dengan nilai kelipofilikan yang baik, kelarutan air secara sederhana dan penyerapan gastrousus yang tinggi. Selain itu, ligan ini tidak melanggar sebarang hukum persamaan drug juga tidak memberi sebarang amaran PAINS dan Brenk, menjustifikasikan ia mempunyai ciri-ciri sebagai drug. Oleh itu, adalah wajar untuk menjalankan kajian lanjutan yang lebih dalam mengenai struktur ini secara in silico, in vitro dan in vivo ke arah pencarian rawatan terhadap penyakit virus Ebola. 

Kata kunci: ADME; cantuman molekul; protein matriks VP40; virus Ebola

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*Corresponding author; email: kbariyyah@iium.edu.my