Roles and Prospects of Dengue Virus Nonstructural Proteins as Antiviral Targets: An Easy Digest

Norazharuddin, Hannah; Lai, Ngit Shin

doi:10.21315/mjms2018.25.5.2

Cited by 33 publications

(20 citation statements)

References 71 publications

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“…Multiple candidate proteins have been identified with NS proteins being the majority, especially the NS1 protein. [18][19][20][21][22][23] The DENV NS1 protein is a glycoprotein translated by the viral genome in different structural forms (Figure 1.) depending on its location.…”

Section: Current State Of Denguementioning

confidence: 99%

“…Despite the β-ladder having minimal structural functionality, the hydrophobic β-roll plays an important role in the dimerization process of the protein while the wing domain is responsible to connect all the domains together into an integral structure. [18,[6][7][8] Hence, in theory, there is a possibility to design certain peptides that are complementary to these domains with the purpose in intercepting their physiology. [1] Similar methods have been implemented by Huang et al in which peptide-based antimicrobial agents are used on non-structural proteins.…”

Section: Current State Of Denguementioning

confidence: 99%

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Potential of Peptide-Based Non-Structural Protein 1 (NS1) Inhibitor in Obstructing Dengue Virus (DENV) Replication

Asyura¹,

Fauzi²,

Ayub

2021

GMJ

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Introduction: Dengue Virus (DENV) is the pathogen for human dengue fever and is responsible for 390 million infections per year. The viral genome produces about 10 viral protein products, one of them being NS1. The NS1 protein plays a key role in viral replication and stimulation of humoral immune cells, thus being the perfect candidate to create an effective antiviral drug or vaccine for dengue Methods: Dengue Virus (DENV) is the pathogen for human dengue fever and is responsible for 390 million infections per year. The viral genome produces about 10 viral protein products, one of them being NS1. The NS1 protein plays a key role in viral replication and stimulation of humoral immune cells, thus being the perfect candidate to create an effective antiviral drug or vaccine for dengue Conclusion: The review established promising results of using peptide-based intervention on NS1. Further in vivo and randomized controlled trials are advised to solidify the applicability and biosafety of the intervention

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Section: Current State Of Denguementioning

confidence: 99%

Section: Current State Of Denguementioning

confidence: 99%

Potential of Peptide-Based Non-Structural Protein 1 (NS1) Inhibitor in Obstructing Dengue Virus (DENV) Replication

Asyura¹,

Fauzi²,

Ayub

2021

GMJ

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“…The helicase domain of NS3, especially on residues 180-618, contains three sub-domains with distinct structural sequence to identify its resemblance to the helicases of another flavivirus. Separation of double-stranded RNA intermediates occurred during viral RNA synthesis initiated by the ATPase/helicase and NTPase activities of DENV NS3, which is bound at the same active site [55].…”

Section: Dengue Virusmentioning

confidence: 99%

Role of Immunoinformatics in Accelerating Epitope-Based Vaccine Development against Dengue Virus

Alkaff

Saragih

Nasution

et al. 2020

TOBIOCJ

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Dengue Fever (DF) has emerged as a significant public health problem of international concern with its high prevalence in the tropic and subtropical regions. Dengue Virus (DENV), which is the cause of DF, consists of four serotypes of antigenically distinct viruses. The immense variation and limited identity similarity at the amino acid level lead to a problematic challenge in the development of an efficacious vaccine. Fortunately, the extensively available immunological data, the advance in antigenic peptide prediction, and the incorporation of molecular docking and dynamics simulation in immunoinformatics have directed the vaccine development towards the rational design of the epitope-based vaccine. Here, we point out the current state of dengue epidemiology and the recent development in vaccine development. Subsequently, we provide a systematic review of our validated method and tools for B- and T-cell epitope prediction as well as the use of molecular docking and dynamics in evaluating epitope affinity and stability in the discovery of a new tetravalent dengue vaccine through computational epitope-based vaccine design.

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“…NS1 interacts with structural proteins and NS4A-2 K-4B to facilitate the production of infectious virus particles [11,79]. Because of their critical roles in the DENV replication cycle, NS2B, NS3, and NS5 along with NS4B are the main focus to design new inhibitors for antiviral therapy against DENV and other related flaviviruses [80][81][82][83]. Assembled viruses are transported through the trans-Golgi network (TGN) where under acidic conditions, a cellular protease, furin, cleaves pre-M, allowing full maturation of infectious virions that will be finally released via exocytosis [84].…”

Section: Dengue Virus Features: Genomic Organization Structure and mentioning

confidence: 99%

Dengue Immunopathogenesis: A Crosstalk between Host and Viral Factors Leading to Disease: Part I - Dengue Virus Tropism, Host Innate Immune Responses, and Subversion of Antiviral Responses

Puerta-Guardo¹,

Biering²,

Harris³

et al. 2020

Dengue Fever in a One Health Perspective

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Dengue is the most prevalent emerging mosquito-borne viral disease, affecting more than 40% of the human population worldwide. Many symptomatic dengue virus (DENV) infections result in a relatively benign disease course known as dengue fever (DF). However, a small proportion of patients develop severe clinical manifestations, englobed in two main categories known as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Secondary infection with any of the four dengue virus serotypes (DENV1, -2, -3, and -4) is a risk factor to develop severe forms of dengue disease. DSS is primarily characterized by sudden and abrupt endothelial dysfunction, resulting in vascular leak and organ impairment, which may progress to hypovolemic shock and death. Severe DENV disease (DHF/DSS) is thought to follow a complex relationship between distinct immunopathogenic processes involving host and viral factors, such as the serotype cross-reactive antibody-dependent enhancement (ADE), the activation of T cells and complement pathways, the phenomenon of the cytokine storm, and the newly described viral toxin activity of the nonstructural protein 1 (NS1), which together play critical roles in inducing vascular leak and virus pathogenesis. In this chapter that is divided in two parts, we will outline the recent advances in our understanding of DENV pathogenesis, highlighting key viral-host interactions and discussing how these interactions may contribute to DENV immunopathology and the development of vascular leak, a hallmark of severe dengue. Part I will address the general features of the DENV complex, including the virus structure and genome, epidemiology, and clinical outcomes, followed by an updated review of the literature describing the host innate immune strategies as well as the viral mechanisms acting against and in favor of the DENV replication cycle and infection.

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Roles and Prospects of Dengue Virus Nonstructural Proteins as Antiviral Targets: An Easy Digest

Cited by 33 publications

References 71 publications

Potential of Peptide-Based Non-Structural Protein 1 (NS1) Inhibitor in Obstructing Dengue Virus (DENV) Replication

Potential of Peptide-Based Non-Structural Protein 1 (NS1) Inhibitor in Obstructing Dengue Virus (DENV) Replication

Role of Immunoinformatics in Accelerating Epitope-Based Vaccine Development against Dengue Virus

Dengue Immunopathogenesis: A Crosstalk between Host and Viral Factors Leading to Disease: Part I - Dengue Virus Tropism, Host Innate Immune Responses, and Subversion of Antiviral Responses

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