Inhibition of dengue virus infection by small interfering RNAs that target highly conserved sequences in the NS4B or NS5 coding regions

Villegas, Paula M; Soto, Elizabeth Ortega; Villa‐Tanaca, Lourdes; Barrón, Blanca Lilia; Torres-Flores, Jesús

doi:10.1007/s00705-018-3757-2

Cited by 13 publications

(7 citation statements)

References 24 publications

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“…Of particular interest is the possibility that nucleotide sequences from the 5'UTR are crucial in enabling YFV to propagate in primates and/or mosquitoes. Although no experiments have thus far reported systematically investigating the constancy of nucleotides in the 5'UTR, the effectiveness of the varieties of small interfering RNA in the control of virus infection is a field of active investigation (21)(22)(23)(24)(25). Should suitable conditions be found in which 5'UTR nucleotide sequences are determined to be inhibitory to YFV, parenteral delivery methods of the relevant inhibitory nucleotides would need to be developed to achieve a therapeutic effect.…”

Section: Discussionmentioning

confidence: 99%

Constancy and Change in the 5’UTR of Yellow Fever Virus

Seligman

2020

Preprint

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The nucleotide composition of the 5’UTR of the yellow fever virus (YFV) has been reported to be the most constant sequence in the viral genome, but a comprehensive analysis of this constancy has not been presented. The current report is an analysis of the 5’UTRs from 48 sequences deposited in GenBank representing the seven described genotypes, five in Africa and two in the Americas. The YFV 5’UTRs consist of 118-120 nucleotides, 92% (110/119) of which are constant in all sequences. The constancy is impressive and suggests that many participate in significant viral functions. Remarkably, analysis of the non-constant nucleotides revealed that in some instances the non-constant nucleotide changes persisted in one or a restricted number of related genotypes and were from sequences isolated over a considerable span of years. This constant feature of non-constant nucleotides is consistent with the concept that the changes were in response to different environmental features such as changes in mosquito hosts or animal reservoirs, particularly as a consequence of spread of YFV from Africa to the New World. Constancy of 5’UTR in general may be helpful in distinction of viral species. Lastly, the presence of sequences of constant nucleotides greater than 19 nucleotides suggests regions of the 5’UTR that may be exploited for use as non-codon RNA as treatment and diagnostic agents in a variety of viral diseases.ImportanceThe 5’UTR is arguably the most neglected portion of the viral genome. It is frequently incomplete in the sequences deposited as otherwise complete sequences in GenBank. The current report is an analysis of complete 5’UTR sequences selected from those deposited in GenBank and indicates that the 5’UTR is 92% conserved confirming that it is a highly conserved portion of the viral genome and suggesting that each conserved nucleotide may be functionally significant. Repeated occurrences of even non-constant nucleotides belong to a restricted number of genotypes raising the possibility that adaptation to new mosquito hosts and animal reservoirs such as those that accompanied spread of yellow fever virus from Africa to the Western Hemisphere are relevant. Knowledge of prolonged strings of invariable nucleotides in the 5’UTR has been used in designing a method for detecting YFV and may also be relevant for designing sequences for viral control of a variety of viruses.

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Section: Discussionmentioning

confidence: 99%

Constancy and Change in the 5’UTR of Yellow Fever Virus

Seligman

2020

Preprint

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“…The RNAi mechanism giving rise to antiviral siRNAs was first discovered using the single-stranded negative-sense RNA respiratory syncytial virus (RSV), a human pneumovirus causing respiratory tract infections [47] . Great efforts were then made to develop siRNA-based viral vaccines against DNA and RNA viruses [48] , [49] , [50] , [51] .…”

Section: Virusesmentioning

confidence: 99%

GalNAc-siRNA conjugates: Prospective tools on the frontier of anti-viral therapeutics

Thangamani

Balasubramanian

Easwaran

et al. 2021

Pharmacological Research

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The growing use of short-interfering RNA (siRNA)-based therapeutics for viral diseases reflects the most recent innovations in anti-viral vaccines and drugs. These drugs play crucial roles in the fight against many hitherto incurable diseases, the causes, pathophysiologies, and molecular processes of which remain unknown. Targeted liver drug delivery systems are in clinical trials. The receptor-mediated endocytosis approach involving the abundant asialoglycoprotein receptors (ASGPRs) on the surfaces of liver cells show great promise. We here review N -acetylgalactosamine (GalNAc)-siRNA conjugates that treat viral diseases such as hepatitis B infection, but we also mention that novel, native conjugate-based, targeted siRNA anti-viral drugs may also cure several life-threatening diseases such as hemorrhagic cystitis, multifocal leukoencephalopathy, and severe acute respiratory syndrome caused by coronaviruses and human herpes virus.

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“…The FG-siRNAs were effective against DENV-1, -3, and -4, but not DENV-2. siRNA specifically targeting the NS5 region of the DENV-2 genome (SG-siRNA) was designed and tested against two different DENV-2 strains, showing high levels of inhibition in both mammalian and insect cells [ 33 ].…”

Section: Inhibitory Effect Of Sirna On Dengue Virus Replicationmentioning

confidence: 99%

Effect of siRNA targeting dengue virus genes on replication of dengue virus: an in vitro experimental study

et al. 2021

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Dengue is a notorious viral infection, which affects a large segment of world populations in absence of vaccines and anti-viral treatment. The current study evaluates role of effective siRNA in dengue virus replication. Eight siRNA were synthesized against five different genes (Capsid, CprM, NS1, NS3 and NS5) of all serotypes of dengue virus. All serotype of DV were transfected with all synthesized siRNA in vitro, using BHK-21 cell lines. Culture fluid from test and control was tested by Real time PCR for CT value comparison in siRNA treated cell line (test) and untreated cell line (controls). Percent knockdown (%KD) was calculated by ∆∆C T methods to know the difference in test and control CT value. It was found that siRNA targeted against capsid gene worked best and showed inhibition of all four DV serotypes. DV-1, DV-2, DV-3 and DV-4 showed 93.8%, 99.3%, 87.5% and 93.8% knock down (%KD) respectively by siRNA targeted against capsid gene. Additionally, Si2 (target CprM gene 60-899) and Si 6 (target NS1 gene 3007-3025) were also showing inhibition of replication. Most serotypes of DV (with few exceptions) were not inhibited by siRNA targeted against NS-1, NS-3, and NS-5 genes. Animal studies using siRNAs are warranted to establish their therapeutic role.

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Inhibition of dengue virus infection by small interfering RNAs that target highly conserved sequences in the NS4B or NS5 coding regions

Cited by 13 publications

References 24 publications

Constancy and Change in the 5’UTR of Yellow Fever Virus

Constancy and Change in the 5’UTR of Yellow Fever Virus

GalNAc-siRNA conjugates: Prospective tools on the frontier of anti-viral therapeutics

Effect of siRNA targeting dengue virus genes on replication of dengue virus: an in vitro experimental study

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