Analogues of 2-Deoxyglucose as inhibitor candidates for hexokinase II identified via virtual screening analyses

Dengue fever is one of the major global health issues, yet specific treatment remains vague. The human hexokinase isoform II (HK2) is one of the crucial enzyme for dengue virus (DENV) replication and thus has been suggested as a potential therapeutic target for DENV drug development. In this paper...

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Main Authors:	Tanbin, Suriyea, Ogu Salim, Nurhainis, Ahmad Fuad, Fazia Adyani
Format:	Conference or Workshop Item
Language:	English
Published:	Kulliyyah of Engineering, International Islamic University Malaysia 2018
Subjects:	TP248.13 Biotechnology
Online Access:	http://irep.iium.edu.my/70506/ http://irep.iium.edu.my/70506/ http://irep.iium.edu.my/70506/1/70506_Analogues%20of%202-Deoxyglucose%20as%20Inhibitor%20Candidates.pdf

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spelling	iium-705062019-02-27T05:43:07Z http://irep.iium.edu.my/70506/ Analogues of 2-Deoxyglucose as inhibitor candidates for hexokinase II identified via virtual screening analyses Tanbin, Suriyea Ogu Salim, Nurhainis Ahmad Fuad, Fazia Adyani TP248.13 Biotechnology Dengue fever is one of the major global health issues, yet specific treatment remains vague. The human hexokinase isoform II (HK2) is one of the crucial enzyme for dengue virus (DENV) replication and thus has been suggested as a potential therapeutic target for DENV drug development. In this paper, compounds with potential HK2 inhibitory activity have been identified by using a combination of ligand-based and structurebased virtual screening approaches. In the initial ligand-based approach, a known HK2 inhibitor, 2- Deoxyglucose (2-DG) was used as the query molecule, which resulted in the identification of analogues of 2-DG with scores ranging from 0.739-0.763. The analogues were docked against the crystal structure of HK2 (PDB ID: 2NZT) in complex with alpha-D-glucose (GLC) and beta-D-glucose-6-phosphate (BG6) by using Auto Dock 4 programme, on chain B where the active sites were located. The docking hits exhibited binding energy ranging from -7.63 to -4.98kcal/mol. Six top-ranked compounds which are most similar to 2-DG were subsequently analysed based on their predicted binding affinity with the catalytic residues (Thr620, Lys621, Asn656, Lys618, Asp657, Phe604, Asn735, Glu629, Gly710, Gly622 and Glu708), H bond analysis and toxicity effect. Among the selected top six compounds, only compound 4 (ZINC26898487) is non-toxicant and has shown good binding energy (-7.63 kcal/mol) relative to 2-DG and contains four H bonds; two with Lys621, one with Glu629 and another one with is Thr620. Meanwhile, the binding energy of 2-DG itself is -7.40kcal/mol when in complex with HK2, with two H bonds; one with Lys621 and another one with Glu708. In this drug design computational studies, compound 4 (ZINC26898487) is suggested to have potentials to inhibit HK2 activity relative to the known inhibitor (2-DG), thus pave the way towards the discovery of new dengue therapeutics Kulliyyah of Engineering, International Islamic University Malaysia 2018 Conference or Workshop Item PeerReviewed application/pdf en http://irep.iium.edu.my/70506/1/70506_Analogues%20of%202-Deoxyglucose%20as%20Inhibitor%20Candidates.pdf Tanbin, Suriyea and Ogu Salim, Nurhainis and Ahmad Fuad, Fazia Adyani (2018) Analogues of 2-Deoxyglucose as inhibitor candidates for hexokinase II identified via virtual screening analyses. In: 5th International Conference on Biotechnology Engineering (ICBioE 2018), 19th-20th September 2018, Kuala Lumpur. http://www.iium.edu.my/icbioe/2018/
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	TP248.13 Biotechnology
spellingShingle	TP248.13 Biotechnology Tanbin, Suriyea Ogu Salim, Nurhainis Ahmad Fuad, Fazia Adyani Analogues of 2-Deoxyglucose as inhibitor candidates for hexokinase II identified via virtual screening analyses
description	Dengue fever is one of the major global health issues, yet specific treatment remains vague. The human hexokinase isoform II (HK2) is one of the crucial enzyme for dengue virus (DENV) replication and thus has been suggested as a potential therapeutic target for DENV drug development. In this paper, compounds with potential HK2 inhibitory activity have been identified by using a combination of ligand-based and structurebased virtual screening approaches. In the initial ligand-based approach, a known HK2 inhibitor, 2- Deoxyglucose (2-DG) was used as the query molecule, which resulted in the identification of analogues of 2-DG with scores ranging from 0.739-0.763. The analogues were docked against the crystal structure of HK2 (PDB ID: 2NZT) in complex with alpha-D-glucose (GLC) and beta-D-glucose-6-phosphate (BG6) by using Auto Dock 4 programme, on chain B where the active sites were located. The docking hits exhibited binding energy ranging from -7.63 to -4.98kcal/mol. Six top-ranked compounds which are most similar to 2-DG were subsequently analysed based on their predicted binding affinity with the catalytic residues (Thr620, Lys621, Asn656, Lys618, Asp657, Phe604, Asn735, Glu629, Gly710, Gly622 and Glu708), H bond analysis and toxicity effect. Among the selected top six compounds, only compound 4 (ZINC26898487) is non-toxicant and has shown good binding energy (-7.63 kcal/mol) relative to 2-DG and contains four H bonds; two with Lys621, one with Glu629 and another one with is Thr620. Meanwhile, the binding energy of 2-DG itself is -7.40kcal/mol when in complex with HK2, with two H bonds; one with Lys621 and another one with Glu708. In this drug design computational studies, compound 4 (ZINC26898487) is suggested to have potentials to inhibit HK2 activity relative to the known inhibitor (2-DG), thus pave the way towards the discovery of new dengue therapeutics
format	Conference or Workshop Item
author	Tanbin, Suriyea Ogu Salim, Nurhainis Ahmad Fuad, Fazia Adyani
author_facet	Tanbin, Suriyea Ogu Salim, Nurhainis Ahmad Fuad, Fazia Adyani
author_sort	Tanbin, Suriyea
title	Analogues of 2-Deoxyglucose as inhibitor candidates for hexokinase II identified via virtual screening analyses
title_short	Analogues of 2-Deoxyglucose as inhibitor candidates for hexokinase II identified via virtual screening analyses
title_full	Analogues of 2-Deoxyglucose as inhibitor candidates for hexokinase II identified via virtual screening analyses
title_fullStr	Analogues of 2-Deoxyglucose as inhibitor candidates for hexokinase II identified via virtual screening analyses
title_full_unstemmed	Analogues of 2-Deoxyglucose as inhibitor candidates for hexokinase II identified via virtual screening analyses
title_sort	analogues of 2-deoxyglucose as inhibitor candidates for hexokinase ii identified via virtual screening analyses
publisher	Kulliyyah of Engineering, International Islamic University Malaysia
publishDate	2018
url	http://irep.iium.edu.my/70506/ http://irep.iium.edu.my/70506/ http://irep.iium.edu.my/70506/1/70506_Analogues%20of%202-Deoxyglucose%20as%20Inhibitor%20Candidates.pdf
first_indexed	2023-09-18T21:40:04Z
last_indexed	2023-09-18T21:40:04Z
_version_	1777413080983011328

Analogues of 2-Deoxyglucose as inhibitor candidates for hexokinase II identified via virtual screening analyses

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