Abstract
In addition to the protein coding information, viral RNA genomes code functional information in structurally conserved units termed functional RNA domains. These RNA domains play essential roles in the viral cycle (e.g., replication and translation). Understanding the molecular mechanisms behind their function is essential to understanding the viral infective cycle. Further, interfering with the function of the genomic RNA domains offers a potential means of developing antiviral strategies. Aptamers are good candidates for targeting structural RNA domains. Besides its potential as therapeutics, aptamers also provide an excellent tool for investigating the functionality of RNA domains in viral genomes. This review briefly summarizes the work carried out in our laboratory aimed at the structural and functional characterization of the hepatitis C virus (HCV) genomic RNA domains. It also describes the efforts we carried out for the development of antiviral aptamers targeting specific genomic domains of the HCV and the human immunodeficiency virus type-1 (HIV-1).
Highlights
The biological function of RNA has, for long time, been considered to be restricted to its role in the transmission of genetic information from DNA to proteins
This review focuses on the hepatitis C virus (HCV) genome, paying special attention to the work carried out in our laboratory aimed at the structural and functional characterization of genomic RNA domains
The second part of the review summarizes the main strategies we have developed seeking aptamers targeted against specific genomic RNA domains of the HCV and HIV genomes
Summary
The biological function of RNA has, for long time, been considered to be restricted to its role in the transmission of genetic information from DNA to proteins. The current information indicates that structural RNA domains play out their different biological roles (e.g., in replication, translation, or encapsidation) by directly recruiting viral and/or cellular factors and/or by forming high-order structures via the establishment of long-range RNA–RNA interaction networks (for a review, see Reference [3]) The essentiality of these genomic RNA domains for the virus makes them excellent candidates as targets for the development of antiviral strategies. The family comprises three genera: Flavivirus, that includes important human pathogens like Dengue virus (DENV), West Nile virus (WNV), yellow fever virus (YFV), or Zika virus (ZIKV), among many others; Pestivirus, represented by the virus responsible of the Bovine viral diarrhea (BVDV) or the classic swine fever (CSFV); and Hepacivirus, with the hepatitis C virus (HCV) as the most significant member Their genome contains multiple highly conserved structural RNA domains, which store essential information for the completion of the viral cycle. The second part of the review summarizes the main strategies we have developed seeking aptamers targeted against specific genomic RNA domains of the HCV and HIV genomes
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