Dengue Virus Non-Structural Protein 5

Sahili, Abbas El; Lescar, Julien

doi:10.3390/v9040091

Cited by 112 publications

(73 citation statements)

References 106 publications

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“…Dengue virus (DENV), a mosquitoborne, positive-strand RNA virus from the family Flaviviridae, has emerged as one of the major public health concerns in India and recent estimates suggest that over 60 million people globally get infected with DENV every year (10). The crystal structures of NS5 protein of DENV and West Nile virus have identified zinc binding site in RdRp domain and propose an important structural role for zinc ions in polymerase activity (11,12). Therefore, zinc is likely to play a prominent role in the polymerase activity of DENV.…”

Section: Introductionmentioning

confidence: 99%

Zinc Chelation Specifically Inhibits Early Stages of Dengue Virus Replication by Activation of NF-κB and Induction of Antiviral Response in Epithelial Cells

et al. 2019

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Zinc is an essential micronutrient which regulates diverse physiological functions and has been shown to play a crucial role in viral infections. Zinc has a necessary role in the replication of many viruses, however, antiviral action of zinc has also been demonstrated in in vitro infection models most likely through induction of host antiviral responses. Therefore, depending on the host machinery that the virus employs at different stages of infection, zinc may either facilitate, or inhibit virus infection. In this study, we show that zinc plays divergent roles in rotavirus and dengue virus infections in epithelial cells. Dengue virus infection did not perturb the epithelial barrier functions despite the release of virus from the basolateral surface whereas rotavirus infection led to disruption of epithelial junctions. In rotavirus infection, zinc supplementation post-infection did not block barrier disruption suggesting that zinc does not affect rotavirus life-cycle or protects epithelial barriers post-infection suggesting the involvement of cellular pathways in the beneficial effect of zinc supplementation in enteric infections. Zinc depletion by N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN) inhibited dengue virus and Japanese encephalitis virus (JEV) infection but had no effect on rotavirus. Time-of-addition experiments suggested that zinc chelation affected both early and late stages of dengue virus infectious cycle and zinc chelation abrogated dengue virus RNA replication. We show that transient zinc chelation induces ER stress and antiviral response by activating NF-kappaB leading to induction of interferon signaling. These results suggest that modulation of zinc homeostasis during virus infection could be a component of host antiviral response and altering zinc homeostasis may act as a potent antiviral strategy against flaviviruses.

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Section: Introductionmentioning

confidence: 99%

Zinc Chelation Specifically Inhibits Early Stages of Dengue Virus Replication by Activation of NF-κB and Induction of Antiviral Response in Epithelial Cells

et al. 2019

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“…Among all the proteins of dengue virus, RNA-dependent RNA polymerase (RdRp) is encoded by non-structural gene NS5 and consists of 20 important enzymatic activities needed for viral propagation. Studies have been conducted on RdRp for designing drug against dengue virus as it is known to be the largest and highly conserved protein (Noble et al, 2010;Noble et al, 2013;El Sahili and Lescar, 2017;Lim et al, 2015). Conserved motif 'YQNKVVRVQRPAKNGTVM-DVISSRDQRGSGQVGTYGLNTFTNMEAQLIRQ' was found in NS5 ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Highly conserved epitopes of DENV structural and non-structural proteins: Candidates for universal vaccine targets

Verma

Bhatnagar

Kumari

et al. 2019

Gene

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A B S T R A C TDengue is a severe emerging arthropod borne viral disease occurring globally. Around two fifths of the world's population, or up to 3.9 billion people, are at a risk of dengue infection. Infection induces a life-long protective immunity to the homologous serotype but confers only partial and transient protection against subsequent infection caused by other serotypes. Thus, there is a need for a vaccine which is capable of providing a life-long protection against all the serotypes of dengue virus.In our study, comparative genomics of Dengue virus (DENV) was conducted to explore potential candidates for novel vaccine targets. From our analysis we successfully found 100% conserved epitopes in Envelope protein (RCPTQGE); NS3 (SAAQRRGR, PGTSGSPI); NS4A (QRTPQDNQL); NS4B (LQAKATREAQKRA) and NS5 proteins (QRGSGQV) in all DENV serotypes. Some serotype specific conserved motifs were also found in NS1, NS5, Capsid, PrM and Envelope proteins. Using comparative genomics and immunoinformatics approach, we could find conserved epitopes which can be explored as peptide vaccine candidates to combat dengue worldwide. Serotype specific epitopes can also be exploited for rapid diagnostics. All ten proteins are explored to find the conserved epitopes in DENV serotypes, thus making it the most extensively studied viral genome so far.

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“…The E protein has been implicated in the membrane fusion between host cells and DENV particles [11]. Importantly, non-structural proteins regulate various stages of the DENV lifecycle, including viral RNA replication, virion assembly, polyprotein cleavage, maturation, and defense against host immunity [12][13][14][15]. Antiviral development approaches thus far have targeted both structural and non-structural proteins, with the main focus on multifunctional enzymes such as NS3, NS4B and NS5 [16][17][18][19][20].…”

Section: Denv Genome and Encoded Proteinsmentioning

confidence: 99%

Structure-Based Design of Antivirals against Envelope Glycoprotein of Dengue Virus

Anasir

Ramanathan

Poh

2020

Viruses

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Dengue virus (DENV) presents a significant threat to global public health with more than 500,000 hospitalizations and 25,000 deaths annually. Currently, there is no clinically approved antiviral drug to treat DENV infection. The envelope (E) glycoprotein of DENV is a promising target for drug discovery as the E protein is important for viral attachment and fusion. Understanding the structure and function of DENV E protein has led to the exploration of structure-based drug discovery of antiviral compounds and peptides against DENV infections. This review summarizes the structural information of the DENV E protein with regards to DENV attachment and fusion. The information enables the development of antiviral agents through structure-based approaches. In addition, this review compares the potency of antivirals targeting the E protein with the antivirals targeting DENV multifunctional enzymes, repurposed drugs and clinically approved antiviral drugs. None of the current DENV antiviral candidates possess potency similar to the approved antiviral drugs which indicates that more efforts and resources must be invested before an effective DENV drug materializes.

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Dengue Virus Non-Structural Protein 5

Cited by 112 publications

References 106 publications

Zinc Chelation Specifically Inhibits Early Stages of Dengue Virus Replication by Activation of NF-κB and Induction of Antiviral Response in Epithelial Cells

Zinc Chelation Specifically Inhibits Early Stages of Dengue Virus Replication by Activation of NF-κB and Induction of Antiviral Response in Epithelial Cells

Highly conserved epitopes of DENV structural and non-structural proteins: Candidates for universal vaccine targets

Structure-Based Design of Antivirals against Envelope Glycoprotein of Dengue Virus

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