scholarly journals G-Quadruplex Targeting in the Fight against Viruses: An Update

2021 ◽  
Vol 22 (20) ◽  
pp. 10984
Author(s):  
Emanuela Ruggiero ◽  
Irene Zanin ◽  
Marianna Terreri ◽  
Sara N. Richter
Keyword(s):  
Life Cycle ◽  
Anticancer Therapy ◽  
Emerging Diseases ◽  
Viral Genomes ◽  
Cellular Processes ◽  
G Quadruplex ◽  
Fast Pace ◽  
Nucleic Acid Structures ◽  
Transcription And Replication

G-quadruplexes (G4s) are noncanonical nucleic acid structures involved in the regulation of key cellular processes, such as transcription and replication. Since their discovery, G4s have been mainly investigated for their role in cancer and as targets in anticancer therapy. More recently, exploration of the presence and role of G4s in viral genomes has led to the discovery of G4-regulated key viral pathways. In this context, employment of selective G4 ligands has helped to understand the complexity of G4-mediated mechanisms in the viral life cycle, and highlighted the possibility to target viral G4s as an emerging antiviral approach. Research in this field is growing at a fast pace, providing increasing evidence of the antiviral activity of old and new G4 ligands. This review aims to provide a punctual update on the literature on G4 ligands exploited in virology. Different classes of G4 binders are described, with emphasis on possible antiviral applications in emerging diseases, such as the current COVID-19 pandemic. Strengths and weaknesses of G4 targeting in viruses are discussed.

Emerging Role of G-quadruplex DNA as Target in Anticancer Therapy

2017 ◽  
Vol 22 (44) ◽  
pp. 6612-6624 ◽  
Author(s):  
Graziella Cimino-Reale ◽  
Nadia Zaffaroni ◽  
Marco Folini
Keyword(s):  
Anticancer Therapy ◽  
Quadruplex Dna ◽  
G Quadruplex

scholarly journals Role of Virally-Encoded Deubiquitinating Enzymes in Regulation of the Virus Life Cycle

2021 ◽  
Vol 22 (9) ◽  
pp. 4438
Author(s):  
Jessica Proulx ◽  
Kathleen Borgmann ◽  
In-Woo Park
Keyword(s):  
Immune Response ◽  
Life Cycle ◽  
Deubiquitinating Enzyme ◽  
Deubiquitinating Enzymes ◽  
Antiviral Immune Response ◽  
Cellular Processes ◽  
Virus Life Cycle ◽  
Infected Cells ◽  
Dependent Processes

The ubiquitin (Ub) proteasome system (UPS) plays a pivotal role in regulation of numerous cellular processes, including innate and adaptive immune responses that are essential for restriction of the virus life cycle in the infected cells. Deubiquitination by the deubiquitinating enzyme, deubiquitinase (DUB), is a reversible molecular process to remove Ub or Ub chains from the target proteins. Deubiquitination is an integral strategy within the UPS in regulating survival and proliferation of the infecting virus and the virus-invaded cells. Many viruses in the infected cells are reported to encode viral DUB, and these vial DUBs actively disrupt cellular Ub-dependent processes to suppress host antiviral immune response, enhancing virus replication and thus proliferation. This review surveys the types of DUBs encoded by different viruses and their molecular processes for how the infecting viruses take advantage of the DUB system to evade the host immune response and expedite their replication.

scholarly journals The Presence and Localization of G-Quadruplex Forming Sequences in the Domain of Bacteria

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1711 ◽  
Author(s):  
Martin Bartas ◽  
Michaela Čutová ◽  
Václav Brázda ◽  
Patrik Kaura ◽  
Jiří Šťastný ◽  
...  
Keyword(s):  
Regulatory Sequences ◽  
Bacterial Genomes ◽  
Dna Structures ◽  
Cellular Processes ◽  
G Quadruplex ◽  
Data Point ◽  
Functional Relevance

The role of local DNA structures in the regulation of basic cellular processes is an emerging field of research. Amongst local non-B DNA structures, the significance of G-quadruplexes was demonstrated in the last decade, and their presence and functional relevance has been demonstrated in many genomes, including humans. In this study, we analyzed the presence and locations of G-quadruplex-forming sequences by G4Hunter in all complete bacterial genomes available in the NCBI database. G-quadruplex-forming sequences were identified in all species, however the frequency differed significantly across evolutionary groups. The highest frequency of G-quadruplex forming sequences was detected in the subgroup Deinococcus-Thermus, and the lowest frequency in Thermotogae. G-quadruplex forming sequences are non-randomly distributed and are favored in various evolutionary groups. G-quadruplex-forming sequences are enriched in ncRNA segments followed by mRNAs. Analyses of surrounding sequences showed G-quadruplex-forming sequences around tRNA and regulatory sequences. These data point to the unique and non-random localization of G-quadruplex-forming sequences in bacterial genomes.

scholarly journals Overview of RNA G-quadruplex structures

2017 ◽  
Vol 63 (4) ◽  
Author(s):  
Magdalena Małgowska
Keyword(s):  
Three Dimensional ◽  
Telomere Maintenance ◽  
Structural Studies ◽  
Biological Functions ◽  
Cellular Processes ◽  
Novel Drugs ◽  
G Quadruplex ◽  
Conformational Diversity

G-quadruplexes are non-canonical secondary structures which may be formed by guanine rich sequences, both in vitro and in living cells. The number of biological functions assigned to these structural motifs has grown rapidly since the discovery of their involvement in the telomere maintenance. Knowledge of the three-dimensional structures of G-quadruplexes plays an important role in understanding their conformational diversity, physiological functions, and in the design of novel drugs targeting G-quadruplexes. For the last decades, structural studies have been mainly focused on the DNA G-quadruplexes. Their RNA counterparts gained an increased interest along with still-emerging recognition of the central role of RNA in multiple cellular processes. In this review we focus on structural properties of RNA G-quadruplexes, based on high-resolution structures, available in RCSB PDB data base and on structural models. In addition, we point out to the current challenges in this field of research.

scholarly journals Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide–quadruplex complex

2015 ◽  
Vol 112 (31) ◽  
pp. 9608-9613 ◽  
Author(s):  
Brahim Heddi ◽  
Vee Vee Cheong ◽  
Herry Martadinata ◽  
Anh Tuân Phan
Keyword(s):  
Electrostatic Interactions ◽  
Solution Structure ◽  
Binding Mode ◽  
Structural Basis ◽  
Cellular Processes ◽  
Charged Amino Acids ◽  
G Quadruplex ◽  
Guanine Base ◽  
Nucleic Acid Structures ◽  
Phosphate Groups

Four-stranded nucleic acid structures called G-quadruplexes have been associated with important cellular processes, which should require G-quadruplex–protein interaction. However, the structural basis for specific G-quadruplex recognition by proteins has not been understood. The DEAH (Asp-Glu-Ala-His) box RNA helicase associated with AU-rich element (RHAU) (also named DHX36 or G4R1) specifically binds to and resolves parallel-stranded G-quadruplexes. Here we identified an 18-amino acid G-quadruplex-binding domain of RHAU and determined the structure of this peptide bound to a parallel DNA G-quadruplex. Our structure explains how RHAU specifically recognizes parallel G-quadruplexes. The peptide covers a terminal guanine base tetrad (G-tetrad), and clamps the G-quadruplex using three-anchor-point electrostatic interactions between three positively charged amino acids and negatively charged phosphate groups. This binding mode is strikingly similar to that of most ligands selected for specific G-quadruplex targeting. Binding to an exposed G-tetrad represents a simple and efficient way to specifically target G-quadruplex structures.

scholarly journals A glance on anti-viral strategy target Coronavirus life cycle

2020 ◽  
Vol 9 (1) ◽  
pp. 1-22
Author(s):  
Yue Zhang ◽  
Huijie Chen ◽  
Nicole Pirozzi ◽  
Yingying Cong
Keyword(s):  
Life Cycle ◽  
Rna Virus ◽  
Spinous Process ◽  
Antiviral Drug ◽  
Host Cells ◽  
Virion Assembly ◽  
Prevention Therapy ◽  
Genome Transcription ◽  
Transcription And Replication

Coronavirus (CoV), is a single-stranded positive-sense RNA virus, which is characterized by a coronal-shaped spinous process on its surface and is the largest known RNA virus. Recently, the new outbreak of CoV was first found in Wuhan, China at the end of 2019, however, the infection is worldwide and causing high pathogenicity and mortality rates, especially in the aged population. Unfortunately, there is no available strategy to control the infection or treat patients. By reviewing the life cycle of CoV infection in host cells, including: virion attachment and entry, genome transcription and replication, and virion assembly and release, we focused on the role of viral proteins in the viral life cycle and summarized how their function could be targeted for the prevention/therapy of CoV. Thus, this information would pave the way to precisely design the antiviral drug component/vaccine against CoVs.

scholarly journals The Potential of Telomeric G-Quadruplexes Containing Modified Oligoguanosine Overhangs in Activation of Bacterial Phagocytosis and Leukotriene Synthesis in Human Neutrophils

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 249 ◽  
Author(s):  
Ekaterina A. Golenkina ◽  
Galina M. Viryasova ◽  
Nina G. Dolinnaya ◽  
Valeria A. Bannikova ◽  
Tatjana V. Gaponova ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Viral Infections ◽  
Uv Spectroscopy ◽  
Human Neutrophils ◽  
First Line ◽  
Cellular Effects ◽  
Cellular Processes ◽  
G Quadruplex ◽  
New Generation

Human neutrophils are the first line of defense against bacterial and viral infections. They eliminate pathogens through phagocytosis, which activate the 5-lipoxygenase (5-LOX) pathway resulting in synthesis of leukotrienes. Using HPLC analysis, flow cytometry, and other biochemical methods, we studied the effect of synthetic oligodeoxyribonucleotides (ODNs) able to fold into G-quadruplex structures on the main functions of neutrophils. Designed ODNs contained four human telomere TTAGGG repeats (G4) including those with phosphorothioate oligoguanosines attached to the end(s) of G-quadruplex core. Just modified analogues of G4 was shown to more actively than parent ODN penetrate into cells, improve phagocytosis of Salmonella typhimurium bacteria, affect 5-LOX activation, the cytosol calcium ion level, and the oxidative status of neutrophils. As evident from CD and UV spectroscopy data, the presence of oligoguanosines flanking G4 sequence leads to dramatic changes in G-quadruplex topology. While G4 folds into a single antiparallel structure, two main folded forms have been identified in solutions of modified ODNs: antiparallel and dominant, more stable parallel. Thus, both the secondary structure of ODNs and their ability to penetrate into the cytoplasm of cells are important for the activation of neutrophil cellular effects. Our results offer new clues for understanding the role of G-quadruplex ligands in regulation of integral cellular processes and for creating the antimicrobial agents of a new generation.

scholarly journals Promise of G-Quadruplex Structure Binding Ligands as Epigenetic Modifiers with Anti-Cancer Effects

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 582 ◽  
Author(s):  
Antara Sengupta ◽  
Akansha Ganguly ◽  
Shantanu Chowdhury
Keyword(s):  
Epigenetic Therapy ◽  
Dna Structures ◽  
Work Support ◽  
Epigenetic Modifiers ◽  
Dna Base ◽  
Anti Cancer ◽  
G Quadruplex ◽  
Cancer Multiple ◽  
Transcription And Replication

Evidences from more than three decades of work support the function of non-duplex DNA structures called G-quadruplex (G4) in important processes like transcription and replication. In addition, G4 structures have been studied in connection with DNA base modifications and chromatin/nucleosome arrangements. Recent work, interestingly, shows promise of G4 structures, through interaction with G4 structure-interacting proteins, in epigenetics—in both DNA and histone modification. Epigenetic changes are found to be intricately associated with initiation as well as progression of cancer. Multiple oncogenes have been reported to harbor the G4 structure at regulatory regions. In this context, G4 structure-binding ligands attain significance as molecules with potential to modify the epigenetic state of chromatin. Here, using examples from recent studies we discuss the emerging role of G4 structures in epigenetic modifications and, therefore, the promise of G4 structure-binding ligands in epigenetic therapy.

scholarly journals Brd4 Is Involved in Multiple Processes of the Bovine Papillomavirus Type 1 Life Cycle

2006 ◽  
Vol 80 (7) ◽  
pp. 3660-3665 ◽  
Author(s):  
Ivar Ilves ◽  
Kristina Mäemets ◽  
Toomas Silla ◽  
Kadri Janikson ◽  
Mart Ustav
Keyword(s):  
Life Cycle ◽  
Transcription Activation ◽  
Bovine Papillomavirus ◽  
Viral Genomes ◽  
Therapeutic Value ◽  
Multiple Processes ◽  
Chromosome Attachment ◽  
Dependent Mechanism

ABSTRACT Brd4 protein has been proposed to act as a cellular receptor for the bovine papillomavirus type 1 (BPV1) E2 protein in the E2-mediated chromosome attachment and mitotic segregation of viral genomes. Here, we provide data that show the involvement of Brd4 in multiple early functions of the BPV1 life cycle, suggest a Brd4-dependent mechanism for E2-dependent transcription activation, and indicate the role of Brd4 in papillomavirus and polyomavirus replication as well as cell-specific utilization of Brd4-linked features in BPV1 DNA replication. Our data also show the potential therapeutic value of the disruption of the E2-Brd4 interaction for the development of antiviral drugs.

scholarly journals Analysis of gene expression and mutation data points on contribution of transcription to the mutagenesis by APOBEC enzymes

NAR Cancer ◽  
2021 ◽  
Vol 3 (3) ◽  
Author(s):  
Almira Chervova ◽  
Bulat Fatykhov ◽  
Alexander Koblov ◽  
Evgeny Shvarov ◽  
Julia Preobrazhenskaya ◽  
...  
Keyword(s):  
Gene Expression ◽  
Whole Genome Sequencing Data ◽  
Sequencing Data ◽  
Induced Mutations ◽  
Cellular Processes ◽  
Human Cancers ◽  
Sense Strand ◽  
Data Points ◽  
Transcription And Replication

Abstract Since the discovery of the role of the APOBEC enzymes in human cancers, the mechanisms of this type of mutagenesis remain little understood. Theoretically, targeting of single-stranded DNA by the APOBEC enzymes could occur during cellular processes leading to the unwinding of DNA double-stranded structure. Some evidence points to the importance of replication in the APOBEC mutagenesis, while the role of transcription is still underexplored. Here, we analyzed gene expression and whole genome sequencing data from five types of human cancers with substantial APOBEC activity to estimate the involvement of transcription in the APOBEC mutagenesis and compare its impact with that of replication. Using the TCN motif as the mutation signature of the APOBEC enzymes, we observed a correlation of active APOBEC mutagenesis with gene expression, confirmed the increase of APOBEC-induced mutations in early-replicating regions and estimated the relative impact of transcription and replication on the APOBEC mutagenesis. We also found that the known effect of higher density of APOBEC-induced mutations on the lagging strand was highest in middle-replicating regions and observed higher APOBEC mutation density on the sense strand, the latter bias positively correlated with the gene expression level.

Sign in / Sign up

Export Citation Format

Share Document