The evolution of antiviral nucleoside analogues: A review for chemists and non-chemists. Part II: Complex modifications to the nucleoside scaffold

Yates, Mary K.; Seley‐Radtke, Katherine L.

doi:10.1016/j.antiviral.2018.11.016

Cited by 207 publications

(204 citation statements)

References 220 publications

(376 reference statements)

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“…The ZIKV replication cycle is closely related to that of other flaviviruses [ 12 ], suggesting the potential for antiflaviral agents to display therapeutic activity also in the case of Zika virus. In this context, antiviral nucleoside analogues are a particularly interesting class of compounds, as they currently represent the most important group of antiviral agents, with roughly 50% of all antiviral drugs on the market belonging to this category [ 13 , 14 ]. With few exceptions, these agents exert their mode of action at the viral polymerase level in their triphosphate form.…”

Section: Introductionmentioning

confidence: 99%

Novel Nucleoside Analogues as Effective Antiviral Agents for Zika Virus Infections

et al. 2020

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Previously considered a neglected flavivirus, Zika virus has recently emerged as a public health concern due to its ability to spread rapidly and cause severe neurological disorders, such as microcephaly in newborn babies from infected mothers, and Guillain-Barré syndrome in adults. Despite extensive efforts towards the identification of effective therapies, specific antivirals are still not available. As part of ongoing medicinal chemistry studies to identify new antiviral agents, we screened against Zika virus replication in vitro in a targeted internal library of small-molecule agents, comprising both nucleoside and non-nucleoside agents. Among the compounds evaluated, novel aryloxyphosphoramidate prodrugs of the nucleosides 2′-C-methyl-adenosine, 2-CMA, and 7-deaza-2′C-methyl-adenosine, 7-DMA, were found to significantly inhibit the virus-induced cytopathic effect in multiple relevant cell lines. In addition, one of these prodrugs exhibits a synergistic antiviral effect against Zika virus when applied in combination with an indirect antiviral agent, a l-dideoxy bicyclic pyrimidine nucleoside analogue, which potently inhibits vaccinia and measles viruses in vitro by targeting a host pathway. Our findings provide a solid basis for further development of an antiviral therapy for Zika virus infections, possibly exploiting a dual approach combining two different agents, one targeting the viral polymerase (direct-acting antiviral), the second targeting a host-directed autophagy mechanism.

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Section: Introductionmentioning

confidence: 99%

Novel Nucleoside Analogues as Effective Antiviral Agents for Zika Virus Infections

et al. 2020

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“…Nucleos(t)ide analogues are much more structurally diverse than their naturally occurring counterparts (Seley-Radtke and Yates, 2018;Yates and Seley-Radtke, 2019). Modifications may be introduced in the nucleobase, the sugar moiety or the phosphate residue.…”

Section: Introductionmentioning

confidence: 99%

Selected nucleos(t)ide-based prescribed drugs and their multi-target activity

Pastuch-Gawołek

Gillner

Król

et al. 2019

European Journal of Pharmacology

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A B S T R A C T Nucleos(t)ide analogues play pivotal roles as antiviral, cytotoxic or immunosuppressive agents. Here, we review recent reports of nucleoside analogues that exhibit broad-spectrum activity towards multiple life-threatening RNA and DNA viruses. We also present a discussion about nucleoside antimetabolites-approved antineoplastic agents-that have recently been shown to have antiviral and/or antibacterial activity. The approved drugs and drug combinations, as well as recently identified candidates for investigation and/or experimentation, are discussed. Several examples of repurposed drugs that have already been approved for use are presented. This strategy can be crucial for the first-line treatment of acute infections or coinfections and for the management of drug-resistant strains.T against viral infections of great medical importance (e.g., herpes simplex virus (HSV), varicella zoster virus (VZV), human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV)) and/or that are known antineoplastic agents used to treat cancer. Approved nucleos(t)ide-based drugs with multi-target activity and compounds being tested in clinical trials or evaluated in preclinical assays are listed in Table 1. In this paper, the term "approval date" means the date on which the drug was approved by the US Food and Drug Administration (FDA) unless otherwise stated. G. Pastuch-Gawołek, et al. Multi-target nucleos(t)ide-based drugs in the treatment and prophylaxis of HIV, HBV and HCV infections

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“…The first lecture was given by Katherine Seley-Radtke (Chemistry), the second lecture was presented by Andrea Brancale (Molecular Modeling) and the third lecture was given by Anthony Keefe (compound library development). The content of Katherine Seley-Radtke's lecture was based on two very recent review articles published by her and one of her Ph.D. students, Mary Yates (Seley-Radtke and Yates and Seley-Radtke, 2019). These articles reviewed the development of nucleoside analogue antiviral drugs, and were written for a target audience of virologists and other non-chemists, as well as chemists who may not be the most familiar with the history of the field.…”

Section: Medicinal Chemistry Symposiummentioning

confidence: 99%