A quest on finding new potential ebola vp40 inhibitors: molecular docking and molecular dynamics simulation studies

Ebola virus is a filamentous virus belonging to Filoviridae family that can cause severe hemorrhagic fever with high fatality rate. Ebola virus matrix protein,VP40 is abundantly expressed during infection and plays several critical roles in oligomerization, budding, viral transcription, and regulati...

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Main Authors:	Mohamad Yussoff, Mohamad Ariff, Abdul Hamid, Azzmer Azzar, Abd Hamid, Shafida, Abd Halim, Khairul Bariyyah
Format:	Conference or Workshop Item
Language:	English
Published:	2018
Subjects:	QD Chemistry
Online Access:	http://irep.iium.edu.my/70646/ http://irep.iium.edu.my/70646/1/70646_A%20QUEST%20ON%20FINDING%20NEW%20POTENTIAL%20EBOLA_complete.pdf

id	iium-70646
recordtype	eprints
spelling	iium-706462019-02-28T08:07:20Z http://irep.iium.edu.my/70646/ A quest on finding new potential ebola vp40 inhibitors: molecular docking and molecular dynamics simulation studies Mohamad Yussoff, Mohamad Ariff Abdul Hamid, Azzmer Azzar Abd Hamid, Shafida Abd Halim, Khairul Bariyyah QD Chemistry Ebola virus is a filamentous virus belonging to Filoviridae family that can cause severe hemorrhagic fever with high fatality rate. Ebola virus matrix protein,VP40 is abundantly expressed during infection and plays several critical roles in oligomerization, budding, viral transcription, and regulation. Interaction of VP40 with RNA is crucial in the early stage of infection to facilitate the transcription of the viral gene. Thus, VP40 is a promising target to inhibit the Ebola virus from spreading. The objective of this study is to identify and optimize ligands that can potentially block RNA binding at the VP40 RNA binding site. A total of 42 compounds from previously studied ligands in the literature were simulated against the RNA binding site using AutoDock Vina. The top ten ligands were then used as templates for similarity search in Zinc databases followed by structured-based virtual screening. The ADMET properties of the compounds were predicted computationally and the binding free energy of the complex was calculated using molecular-mechanics Poisson Boltzmann surface area (MM-PBSA) method to determine the ligands binding affinity. The results showed that Q-88 (ZINC ID: 1342431) is the best ligand with free energy of -97.27 kJ/mol. Our studies revealed that substituting the sulphur (S) atom with oxygen (O) in the backbone structure resulted in better ADME properties with similar binding affinity (-97.097 kJ/mol) against the RNA binding site. Our findings shed light on binding energies and potential modification of previously tested compounds against VP40, which could be useful for the design of new inhibitor of Ebola virus. 2018-11 Conference or Workshop Item NonPeerReviewed application/pdf en http://irep.iium.edu.my/70646/1/70646_A%20QUEST%20ON%20FINDING%20NEW%20POTENTIAL%20EBOLA_complete.pdf Mohamad Yussoff, Mohamad Ariff and Abdul Hamid, Azzmer Azzar and Abd Hamid, Shafida and Abd Halim, Khairul Bariyyah (2018) A quest on finding new potential ebola vp40 inhibitors: molecular docking and molecular dynamics simulation studies. In: Computer-aided Drug Design 2018, 26 - 30 November 2018, Kuta Fave hotel , Bali. (Unpublished)
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	QD Chemistry
spellingShingle	QD Chemistry Mohamad Yussoff, Mohamad Ariff Abdul Hamid, Azzmer Azzar Abd Hamid, Shafida Abd Halim, Khairul Bariyyah A quest on finding new potential ebola vp40 inhibitors: molecular docking and molecular dynamics simulation studies
description	Ebola virus is a filamentous virus belonging to Filoviridae family that can cause severe hemorrhagic fever with high fatality rate. Ebola virus matrix protein,VP40 is abundantly expressed during infection and plays several critical roles in oligomerization, budding, viral transcription, and regulation. Interaction of VP40 with RNA is crucial in the early stage of infection to facilitate the transcription of the viral gene. Thus, VP40 is a promising target to inhibit the Ebola virus from spreading. The objective of this study is to identify and optimize ligands that can potentially block RNA binding at the VP40 RNA binding site. A total of 42 compounds from previously studied ligands in the literature were simulated against the RNA binding site using AutoDock Vina. The top ten ligands were then used as templates for similarity search in Zinc databases followed by structured-based virtual screening. The ADMET properties of the compounds were predicted computationally and the binding free energy of the complex was calculated using molecular-mechanics Poisson Boltzmann surface area (MM-PBSA) method to determine the ligands binding affinity. The results showed that Q-88 (ZINC ID: 1342431) is the best ligand with free energy of -97.27 kJ/mol. Our studies revealed that substituting the sulphur (S) atom with oxygen (O) in the backbone structure resulted in better ADME properties with similar binding affinity (-97.097 kJ/mol) against the RNA binding site. Our findings shed light on binding energies and potential modification of previously tested compounds against VP40, which could be useful for the design of new inhibitor of Ebola virus.
format	Conference or Workshop Item
author	Mohamad Yussoff, Mohamad Ariff Abdul Hamid, Azzmer Azzar Abd Hamid, Shafida Abd Halim, Khairul Bariyyah
author_facet	Mohamad Yussoff, Mohamad Ariff Abdul Hamid, Azzmer Azzar Abd Hamid, Shafida Abd Halim, Khairul Bariyyah
author_sort	Mohamad Yussoff, Mohamad Ariff
title	A quest on finding new potential ebola vp40 inhibitors: molecular docking and molecular dynamics simulation studies
title_short	A quest on finding new potential ebola vp40 inhibitors: molecular docking and molecular dynamics simulation studies
title_full	A quest on finding new potential ebola vp40 inhibitors: molecular docking and molecular dynamics simulation studies
title_fullStr	A quest on finding new potential ebola vp40 inhibitors: molecular docking and molecular dynamics simulation studies
title_full_unstemmed	A quest on finding new potential ebola vp40 inhibitors: molecular docking and molecular dynamics simulation studies
title_sort	quest on finding new potential ebola vp40 inhibitors: molecular docking and molecular dynamics simulation studies
publishDate	2018
url	http://irep.iium.edu.my/70646/ http://irep.iium.edu.my/70646/1/70646_A%20QUEST%20ON%20FINDING%20NEW%20POTENTIAL%20EBOLA_complete.pdf
first_indexed	2023-09-18T21:40:17Z
last_indexed	2023-09-18T21:40:17Z
_version_	1777413094391152640

A quest on finding new potential ebola vp40 inhibitors: molecular docking and molecular dynamics simulation studies

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