Design, synthesis and evaluation of 2′-acetylene-7-deaza-adenosine phosphoamidate derivatives as anti-EV71 and anti-EV-D68 agents

Yan, Lipeng; Cao, Ruiyuan; Zhang, Hongjie; Li, Yuexiang; Li, Wei; Li, Xiaoyuan; Fan, Shiyong; Li, Song; Zhong, Wu

doi:10.1016/j.ejmech.2021.113852

Cited by 4 publications

(3 citation statements)

References 54 publications

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“…The derivative containing a cyclohexyl ester of l-alanine (15 l) showed a high selectivity index (SI) against EV-A71 (IC 50 = 0.19 ± 0.27 μM, SI = 117.00) and EV-D68 (IC 50 = 0.17 ± 0.16 μM, SI = 130.76). The toxicity of these NTD008 derivatives in vivo are yet to be determined [ 93 ].…”

Section: Drugs Acting On 3d Polmentioning

confidence: 99%

The multiple roles of viral 3D ^pol protein in picornavirus infections

Nie,

Zhai,

Zhang

et al. 2024

Virulence

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The Picornaviridae are a large group of positive-sense, single-stranded RNA viruses, and most research has focused on the Enterovirus genus, given they present a severe health risk to humans. Other picornaviruses, such as foot-and-mouth disease virus (FMDV) and senecavirus A (SVA), affect agricultural production with high animal mortality to cause huge economic losses. The 3D pol protein of picornaviruses is widely known to be used for genome replication; however, a growing number of studies have demonstrated its non-polymerase roles, including modulation of host cell biological processes, viral replication complex assembly and localization, autophagy, and innate immune responses. Currently, there is no effective vaccine to control picornavirus diseases widely, and clinical therapeutic strategies have limited efficiency in combating infections. Many efforts have been made to develop different types of drugs to prohibit virus survival; the most important target for drug development is the virus polymerase, a necessary element for virus replication. For picornaviruses, there are also active efforts in targeted 3D pol drug development. This paper reviews the interaction of 3D pol proteins with the host and the progress of drug development targeting 3D pol .

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Section: Drugs Acting On 3d Polmentioning

confidence: 99%

The multiple roles of viral 3D ^pol protein in picornavirus infections

Nie,

Zhai,

Zhang

et al. 2024

Virulence

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“…In this approach, the 5′-phosphate substituent of nucleoside (nucleotide) analogues is masked by an aryl group and an amino acid ester residue. Such a phosphoramidate, which became known as ProTide (PROdrug + nucleoTIDE) [ 27 ] ( Figure 2 ), is able to enter the cell via facilitated passive diffusion or by means of nucleoside transporters and afford a monophosphate form of a parent nucleoside analogue after cleavage of the masking groups via sequence enzyme-mediated and spontaneous steps, including the hydrolysis of the amino acid ester by carboxyesterase or cathepsin A, displacement of the phosphate phenol by the carboxylate anion, chemical hydrolysis, and cleavage of the amino acid moiety by the histidine triad nucleotide-binding protein [ 28 ]. Numerous studies have shown a clear correlation between the nature of aromatic and amino acid moieties and antiviral potency.…”

Section: Introductionmentioning

confidence: 99%

“…Sofosbuvir was approved by the FDA in December 2013 for the treatment of HCV [ 33 ]. Remdesivir, which exhibits a wide range of activities against RNA viruses [ 4 , 28 ], is currently the only FDA-approved antiviral drug for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

The First 5′-Phosphorylated 1,2,3-Triazolyl Nucleoside Analogues with Uracil and Quinazoline-2,4-Dione Moieties: A Synthesis and Antiviral Evaluation

et al. 2022

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A series of 5′-phosphorylated (dialkyl phosphates, diaryl phosphates, phosphoramidates, H-phosphonates, phosphates) 1,2,3-triazolyl nucleoside analogues in which the 1,2,3-triazole-4-yl-β-D-ribofuranose fragment is attached via a methylene group or a butylene chain to the N-1 atom of the heterocycle moiety (uracil or quinazoline-2,4-dione) was synthesized. All compounds were evaluated for antiviral activity against influenza virus A/PR/8/34/(H1N1). Antiviral assays revealed three compounds, 13b, 14b, and 17a, which showed moderate activity against influenza virus A (H1N1) with IC50 values of 17.9 μM, 51 μM, and 25 μM, respectively. In the first two compounds, the quinazoline-2,4-dione moiety is attached via a methylene or a butylene linker, respectively, to the 1,2,3-triazole-4-yl-β-D-ribofuranosyl fragment possessing a 5′-diphenyl phosphate substituent. In compound 17a, the uracil moiety is attached via the methylene unit to the 1,2,3-triazole-4-yl-β-D-ribofuranosyl fragment possessing a 5′-(phenyl methoxy-L-alaninyl)phosphate substituent. The remaining compounds appeared to be inactive against influenza virus A/PR/8/34/(H1N1). The results of molecular docking simulations indirectly confirmed the literature data that the inhibition of viral replication is carried out not by nucleoside analogues themselves, but by their 5′-triphosphate derivatives.

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Synthesis of 10,10′-bis(trifluoromethyl) marinopyrrole A derivatives and evaluation of their antiviral activities in vitro

Xiao

Yang

Zou

et al. 2022

European Journal of Medicinal Chemistry

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Design, synthesis and evaluation of 2′-acetylene-7-deaza-adenosine phosphoamidate derivatives as anti-EV71 and anti-EV-D68 agents

Cited by 4 publications

References 54 publications

The multiple roles of viral 3D ^pol protein in picornavirus infections

The multiple roles of viral 3D ^pol protein in picornavirus infections

The First 5′-Phosphorylated 1,2,3-Triazolyl Nucleoside Analogues with Uracil and Quinazoline-2,4-Dione Moieties: A Synthesis and Antiviral Evaluation

Synthesis of 10,10′-bis(trifluoromethyl) marinopyrrole A derivatives and evaluation of their antiviral activities in vitro

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Design, synthesis and evaluation of 2′-acetylene-7-deaza-adenosine phosphoamidate derivatives as anti-EV71 and anti-EV-D68 agents

Cited by 4 publications

References 54 publications

The multiple roles of viral 3D pol protein in picornavirus infections

The multiple roles of viral 3D pol protein in picornavirus infections

The First 5′-Phosphorylated 1,2,3-Triazolyl Nucleoside Analogues with Uracil and Quinazoline-2,4-Dione Moieties: A Synthesis and Antiviral Evaluation

Synthesis of 10,10′-bis(trifluoromethyl) marinopyrrole A derivatives and evaluation of their antiviral activities in vitro

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The multiple roles of viral 3D ^pol protein in picornavirus infections

The multiple roles of viral 3D ^pol protein in picornavirus infections