DNA Related Enzymes as Molecular Targets for Antiviral and Antitumoral Chemotherapy. A Natural Overview of the Current Perspectives

Garro, Hugo Alejandro; Pungitore, Carlos Rodolfo

doi:10.2174/1389450119666180426103558

Cited by 3 publications

(2 citation statements)

References 82 publications

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“…Of note, several tumor malignancies are associated with viral infections. Then, the anticancer drug-mediated immunomodulating effects on NK cells in response to viral infections should be further evaluated [204].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

DNAM-1 Activating Receptor and Its Ligands: How Do Viruses Affect the NK Cell-Mediated Immune Surveillance during the Various Phases of Infection?

Cifaldi

Doria

Cotugno

et al. 2019

IJMS

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Natural Killer (NK) cells play a critical role in host defense against viral infections. The mechanisms of recognition and killing of virus-infected cells mediated by NK cells are still only partially defined. Several viruses induce, on the surface of target cells, the expression of molecules that are specifically recognized by NK cell-activating receptors. The main NK cell-activating receptors involved in the recognition and killing of virus-infected cells are NKG2D and DNAM-1. In particular, ligands for DNAM-1 are nectin/nectin-like molecules involved also in mechanisms allowing viral infection. Viruses adopt several immune evasion strategies, including those affecting NK cell-mediated immune surveillance, causing persistent viral infection and the development of virus-associated diseases. The virus’s immune evasion efficacy depends on molecules differently expressed during the various phases of infection. In this review, we overview the molecular strategies adopted by viruses, specifically cytomegalovirus (CMV), human immunodeficiency virus (HIV-1), herpes virus (HSV), Epstein-Barr virus (EBV) and hepatitis C virus (HCV), aiming to evade NK cell-mediated surveillance, with a special focus on the modulation of DNAM-1 activating receptor and its ligands in various phases of the viral life cycle. The increasing understanding of mechanisms involved in the modulation of activating ligands, together with those mediating the viral immune evasion strategies, would provide critical tools leading to design novel NK cell-based immunotherapies aiming at viral infection control, thus improving cure strategies of virus-associated diseases.

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Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

DNAM-1 Activating Receptor and Its Ligands: How Do Viruses Affect the NK Cell-Mediated Immune Surveillance during the Various Phases of Infection?

Cifaldi

Doria

Cotugno

et al. 2019

IJMS

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show abstract

“…5 Such DNA replication inhibitors have broad applicability in antiviral and antitumoral chemotherapy. 6 As many potential drug targets lack robust and easily assayable enzymatic activities, biochemical approaches have limitations in HTS. For example, few identified inhibitors block the early stages of DNA replication, as many such initiation factors function as multi-subunit complexes that are difficult to purify in sufficient quantity (e.g., ORC and MCM2-7) or lack enzymatic activity in isolation (CDC45 and the GINS complex).…”

Section: Introductionmentioning

confidence: 99%

A High-Throughput Assay for DNA Replication Inhibitors Based upon Multivariate Analysis of Yeast Growth Kinetics

Ngo

Wechter

Tsai³

et al. 2019

SLAS Discovery

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Mcm2–7 is the molecular motor of eukaryotic replicative helicase, and the regulation of this complex is a major focus of cellular S-phase regulation. Despite its cellular importance, few small-molecule inhibitors of this complex are known. Based upon our genetic analysis of synthetic growth defects between mcm alleles and a range of other alleles, we have developed a high-throughput screening (HTS) assay using a well-characterized mcm mutant (containing the mcm2DENQ allele) to identify small molecules that replicate such synthetic growth defects. During assay development, we found that aphidicolin (inhibitor of DNA polymerase alpha) and XL413 (inhibitor of the DNA replication-dependent kinase CDC7) preferentially inhibited growth of the mcm2DENQ strain relative to the wild-type parental strain. However, as both strains demonstrated some degree of growth inhibition with these compounds, small and variable assay windows can result. To increase assay sensitivity and reproducibility, we developed a strategy combining the analysis of cell growth kinetics with linear discriminant analysis (LDA). We found that LDA greatly improved assay performance and captured a greater range of synthetic growth inhibition phenotypes, yielding a versatile analysis platform conforming to HTS requirements.

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A Comprehensive Comparative Analysis on the Codon Usage Bias of DNA Polymerase Genes in Invertebrate Iridescent Viruses

Aktürk Dizman

2024

Recep Tayyip Erdoğan Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi

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Invertebrate iridescent viruses (IIVs) are classified as double-stranded DNA viruses within the Iridoviridae family. IIVs are viruses that infect invertebrate hosts, causing symptoms that vary in intensity from slight reductions in host fitness to systemic disease. Numerous earlier investigations have provided insights into the genomic, proteomic, and transcriptional analyses of invertebrate iridescent viruses. However, the codon usage bias (CUB) of IIVs has yet to be fully understood. In order to gain a more profound insight into the evolutionary features of IIVs, we conducted an extensive analysis of the codon usage patterns in the DNA polymerase genes (DNA pol genes) of 12 invertebrate iridescent viruses. The analysis of both nucleotide composition and relative synonymous codon usage (RSCU) indicated a higher prevalence of AT-ended codons in the DNA pol genes of IIVs. Additionally, a low codon usage bias was determined from the effective number of codons (ENC) value. Analyses of ENC-GC3s plot, neutrality plot, and parity rule 2 plot illustrated that the codon usage patterns in IIVs DNA pol genes were influenced by both natural selection and mutational pressure. This investigation holds significance as it has delineated the codon usage patterns within the DNA pol genes of IIVs and has furnished crucial data for a foundational study of their evolutionary aspects.

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DNA Related Enzymes as Molecular Targets for Antiviral and Antitumoral Chemotherapy. A Natural Overview of the Current Perspectives

Abstract: The findings of this review confirm the importance to find new drugs and biologically active natural products, and their potential medicinally useful benefits.

Cited by 3 publications

References 82 publications

DNAM-1 Activating Receptor and Its Ligands: How Do Viruses Affect the NK Cell-Mediated Immune Surveillance during the Various Phases of Infection?

DNAM-1 Activating Receptor and Its Ligands: How Do Viruses Affect the NK Cell-Mediated Immune Surveillance during the Various Phases of Infection?

A High-Throughput Assay for DNA Replication Inhibitors Based upon Multivariate Analysis of Yeast Growth Kinetics

A Comprehensive Comparative Analysis on the Codon Usage Bias of DNA Polymerase Genes in Invertebrate Iridescent Viruses

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