Expression Of Recombinant Denv Ns2b/Ns3 Protease: In Silico Screening And In Vitro Validation Of Novel Antiviral Compounds For Dengue Virus Inhibition

Globally, the relentless rise in dengue cases worldwide has been further intensified and inadvertently neglected in the backdrop of the persistent covid-19 pandemic. Despite the escalating global impact of dengue virus (denv) infection, there remains a conspicuous absence of its effective treatme...

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Main Author: Harun, Norshidah
Format: Thesis
Language:English
Published: 2024
Subjects:
Online Access:http://eprints.usm.my/62656/
http://eprints.usm.my/62656/1/24%20Pages%20from%20NORSHIDAH%20BINTI%20HARUN.pdf
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author Harun, Norshidah
author_facet Harun, Norshidah
author_sort Harun, Norshidah
building USM Institutional Repository
collection Online Access
description Globally, the relentless rise in dengue cases worldwide has been further intensified and inadvertently neglected in the backdrop of the persistent covid-19 pandemic. Despite the escalating global impact of dengue virus (denv) infection, there remains a conspicuous absence of its effective treatment. Hence, the exploration and advancement of dengue antiviral treatments remain a primary focus of research. An appealing target for the anti-denv drugs is the virally encoded trypsin-like serine protease (ns3pro) and its related cofactor (ns2b). The denv ns2b/ns3 protease complex is responsible for cleaving the viral polyprotein into distinct functional viral proteins, making it crucial for virus replication. In the past 15 years, the production of an active denv ns2b/ns3 pro has mostly relied on constructs that link the cterminus of the hydrophilic cofactor domain of ns2b to the n-terminus of ns3 pro using a flexible glycine linker. Despite thorough analysis, no potential inhibitory drugs have been discovered thus far. Furthermore, the impact of the synthetic linker introduced between the protease and its cofactor remains uncertain. Recently, an alternative strategy for producing a catalytically active denv ns2b/ns3 pro complex that is not covalently connected has been reported by professor paul young from the university of queensland, australia, and his team. By employing the non-covalent plasmid construct, this study successfully expressed and purified a high-solubility protein of recombinant denv ns2b/ns3 pro under optimal conditions, with betaine supplementation.
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institution Universiti Sains Malaysia
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language English
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spelling usm-626562025-07-22T01:42:08Z http://eprints.usm.my/62656/ Expression Of Recombinant Denv Ns2b/Ns3 Protease: In Silico Screening And In Vitro Validation Of Novel Antiviral Compounds For Dengue Virus Inhibition Harun, Norshidah R5-920 Medicine (General) Globally, the relentless rise in dengue cases worldwide has been further intensified and inadvertently neglected in the backdrop of the persistent covid-19 pandemic. Despite the escalating global impact of dengue virus (denv) infection, there remains a conspicuous absence of its effective treatment. Hence, the exploration and advancement of dengue antiviral treatments remain a primary focus of research. An appealing target for the anti-denv drugs is the virally encoded trypsin-like serine protease (ns3pro) and its related cofactor (ns2b). The denv ns2b/ns3 protease complex is responsible for cleaving the viral polyprotein into distinct functional viral proteins, making it crucial for virus replication. In the past 15 years, the production of an active denv ns2b/ns3 pro has mostly relied on constructs that link the cterminus of the hydrophilic cofactor domain of ns2b to the n-terminus of ns3 pro using a flexible glycine linker. Despite thorough analysis, no potential inhibitory drugs have been discovered thus far. Furthermore, the impact of the synthetic linker introduced between the protease and its cofactor remains uncertain. Recently, an alternative strategy for producing a catalytically active denv ns2b/ns3 pro complex that is not covalently connected has been reported by professor paul young from the university of queensland, australia, and his team. By employing the non-covalent plasmid construct, this study successfully expressed and purified a high-solubility protein of recombinant denv ns2b/ns3 pro under optimal conditions, with betaine supplementation. 2024-05 Thesis NonPeerReviewed application/pdf en http://eprints.usm.my/62656/1/24%20Pages%20from%20NORSHIDAH%20BINTI%20HARUN.pdf Harun, Norshidah (2024) Expression Of Recombinant Denv Ns2b/Ns3 Protease: In Silico Screening And In Vitro Validation Of Novel Antiviral Compounds For Dengue Virus Inhibition. PhD thesis, Perpustakaan Hamzah Sendut.
spellingShingle R5-920 Medicine (General)
Harun, Norshidah
Expression Of Recombinant Denv Ns2b/Ns3 Protease: In Silico Screening And In Vitro Validation Of Novel Antiviral Compounds For Dengue Virus Inhibition
title Expression Of Recombinant Denv Ns2b/Ns3 Protease: In Silico Screening And In Vitro Validation Of Novel Antiviral Compounds For Dengue Virus Inhibition
title_full Expression Of Recombinant Denv Ns2b/Ns3 Protease: In Silico Screening And In Vitro Validation Of Novel Antiviral Compounds For Dengue Virus Inhibition
title_fullStr Expression Of Recombinant Denv Ns2b/Ns3 Protease: In Silico Screening And In Vitro Validation Of Novel Antiviral Compounds For Dengue Virus Inhibition
title_full_unstemmed Expression Of Recombinant Denv Ns2b/Ns3 Protease: In Silico Screening And In Vitro Validation Of Novel Antiviral Compounds For Dengue Virus Inhibition
title_short Expression Of Recombinant Denv Ns2b/Ns3 Protease: In Silico Screening And In Vitro Validation Of Novel Antiviral Compounds For Dengue Virus Inhibition
title_sort expression of recombinant denv ns2b/ns3 protease: in silico screening and in vitro validation of novel antiviral compounds for dengue virus inhibition
topic R5-920 Medicine (General)
url http://eprints.usm.my/62656/
http://eprints.usm.my/62656/1/24%20Pages%20from%20NORSHIDAH%20BINTI%20HARUN.pdf