A highly conserved G-rich consensus sequence in hepatitis C virus core gene represents a new anti–hepatitis C target

Wang, Shaoru; Min, Yuan-Qin; Wang, Jiaqi; Liu, Chaoxing; Fu, Boshi; Wu, Fan; Wu, Lu; Qiao, Zhixian; Song, Yanyan; Xu, Guisheng; Wu, Zhiguo; Huang, Gai; Peng, Nanfang; Huang, Rong; Mao, Weihua; Peng, Shuang; Chen, Yuqi; Zhu, Ying; Tian, Tian; Zhang, Xiaolian; Zhou, Xiang

doi:10.1126/sciadv.1501535

Cited by 114 publications

(118 citation statements)

References 75 publications

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“…A functional purpose for PQSs has also been observed in the herpes simplex virus, 21 the simian virus 40 T-antigen, 22 and the hepatitis C virus that is also in the Flaviviridae family. 23 These studies highlight a critical role for PQSs in viruses and their ability to be targeted with small-molecule drugs. Therefore, as a first step, inspection of the Zika virus genome for PQS sites was conducted.…”

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confidence: 99%

Zika Virus Genomic RNA Possesses Conserved G-Quadruplexes Characteristic of the Flaviviridae Family

et al. 2016

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Zika virus has emerged as a global concern because neither a vaccine nor antiviral compounds targeting it exist. A structure for the positive-sense RNA genome has not been established, leading us to look for potential G-quadruplex sequences (PQS) in the genome. The analysis identified >60 PQSs in the Zika genome. To minimize the PQS population, conserved sequences in the Flaviviridae family were found by sequence alignment, identifying seven PQSs in the prM, E, NS1, NS3, and NS5 genes. Next, alignment of 78 Zika strain genomes identified a unique PQS near the end of the 3′-UTR. Structural studies on the G-quadruplex sequences found four of the conserved Zika virus sequences to adopt stable, parallel-stranded folds that bind a G-quadruplex-specific compound, and one that was studied caused polymerase stalling when folded to a G-quadruplex. Targeting these PQSs with G-quadruplex binding molecules validated in previous clinical trials may represent a new approach for inhibiting viral replication.

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confidence: 99%

Zika Virus Genomic RNA Possesses Conserved G-Quadruplexes Characteristic of the Flaviviridae Family

et al. 2016

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“…G4s have been reported in the SARS coronavirus7, the human papilloma, hepatitis C, Zika and Ebola virus genomes891011. Among herpesviruses, RNA G4s have been implicated in the regulation of DNA replication and translation of the Epstein–Barr virus1213.…”

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confidence: 99%

The cellular protein hnRNP A2/B1 enhances HIV-1 transcription by unfolding LTR promoter G-quadruplexes

Scalabrin

Frasson

Ruggiero

et al. 2017

Sci Rep

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G-quadruplexes are four-stranded conformations of nucleic acids that act as cellular epigenetic regulators. A dynamic G-quadruplex forming region in the HIV-1 LTR promoter represses HIV-1 transcription when in the folded conformation. This activity is enhanced by nucleolin, which induces and stabilizes the HIV-1 LTR G-quadruplexes. In this work by a combined pull-down/mass spectrometry approach, we consistently found hnRNP A2/B1 as an additional LTR-G-quadruplex interacting protein. Surface plasmon resonance confirmed G-quadruplex specificity over linear sequences and fluorescence resonance energy transfer analysis indicated that hnRNP A2/B1 is able to efficiently unfold the LTR G-quadruplexes. Evaluation of the thermal stability of the LTR G-quadruplexes in different-length oligonucleotides showed that the protein is fit to be most active in the LTR full-length environment. When hnRNP A2/B1 was silenced in cells, LTR activity decreased, indicating that the protein acts as a HIV-1 transcription activator. Our data highlight a tightly regulated control of transcription based on G-quadruplex folding/unfolding, which depends on interacting cellular proteins. These findings provide a deeper understanding of the viral transcription mechanism and may pave the way to the development of drugs effective against the integrated HIV-1, present both in actively and latently infected cells.

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“…For an example, ssDNA aptamer ZE2 against HCVsurface glycoprotein E2 has been used in several reports. [184][185][186] Oligonucleotide aptamers are promising candidates for the diagnosis and treatment of infectious diseases.…”

Section: Resultsmentioning

confidence: 99%

Oligonucleotide aptamers: promising and powerful diagnostic and therapeutic tools for infectious diseases

Pan

Liu

Zhang

2018

Journal of Infection

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The entire human population is at risk of infectious diseases worldwide. Thus far, the diagnosis and treatment of human infectious diseases at the molecular and nanoscale levels have been extremely challenging tasks because of the lack of effective probes to identify and recognize biomarkers of pathogens. Oligonucleotide aptamers are a class of small nucleic acid ligands that are composed of single-stranded DNA (ssDNA) or RNA and act as affinity probes or molecular recognition elements for a variety of targets. These aptamers have an exciting potential for diagnose and/or treatment of specific diseases. In this review, we highlight areas where aptamers have been developed as diagnostic and therapeutic agents for both bacterial and viral infectious diseases as well as aptamer-based detection.

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A highly conserved G-rich consensus sequence in hepatitis C virus core gene represents a new anti–hepatitis C target

Abstract: A conserved guanine-rich sequence could be a new target for anti–hepatitis C virus drug development.

Cited by 114 publications

References 75 publications

Zika Virus Genomic RNA Possesses Conserved G-Quadruplexes Characteristic of the Flaviviridae Family

Zika Virus Genomic RNA Possesses Conserved G-Quadruplexes Characteristic of the Flaviviridae Family

The cellular protein hnRNP A2/B1 enhances HIV-1 transcription by unfolding LTR promoter G-quadruplexes

Oligonucleotide aptamers: promising and powerful diagnostic and therapeutic tools for infectious diseases

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