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Related Experiment Video

Updated: Feb 22, 2026

Engineering Antiviral Agents via Surface Plasmon Resonance

Engineering Antiviral Agents via Surface Plasmon Resonance

Published on: June 14, 2022

Anchimerically Activatable Antiviral ProTides.

Aniekan Okon¹, Marcos Romário Matos de Souza², Rachit Shah¹

¹Departments of Medicinal Chemistry and Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, United States.

ACS Medicinal Chemistry Letters

|September 27, 2017

Summary

Researchers developed a novel proTide drug that effectively inhibits dengue virus 2 (DENV-2) replication. This proTide shows enhanced efficacy compared to the parent nucleoside without causing cytotoxicity, highlighting a promising new antiviral strategy.

Keywords:

Dengue virus Phosphoramidate antiviral pronucleotide

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Early Viral Entry Assays for the Identification and Evaluation of Antiviral Compounds

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Published on: October 29, 2015

Area of Science:

Medicinal Chemistry
Virology
Drug Discovery

Background:

Dengue virus 2 (DENV-2) poses a significant global health threat.
Developing effective and safe antiviral therapies for DENV-2 remains a priority.

Purpose of the Study:

To synthesize and evaluate an anchimerically activated proTide of 2'-C-β-methylguanosine as a DENV-2 inhibitor.
To investigate the mechanism of action involving HINT1 (histidine triad nucleotide-binding protein 1).

Main Methods:

Chemical synthesis of a novel proTide incorporating a cleavable 2-(methylthio)ethyl moiety and a HINT1-hydrolyzable tryptamine phosphoramidate.
Biological evaluation of the proTide's inhibitory activity against DENV-2 replication.
Assessment of cytotoxicity and correlation with HINT1 activity using an inhibitor.

Main Results:

The synthesized proTide (compound 6) demonstrated a 5-fold greater inhibition of DENV-2 replication compared to the parent nucleoside.
The proTide exhibited no apparent cytotoxicity.
Anti-DENV-2 activity of the proTide was shown to correlate with HINT1 enzyme activity.

Conclusions:

A novel phosphoramidate-based pronucleotide was successfully prepared.
The pronucleotide utilizes a dual activation mechanism: initial nonenzymatic activation via anchimeric assistance, followed by HINT1-mediated P-N bond cleavage.
This proTide represents a promising strategy for developing new anti-DENV-2 therapeutics.