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Updated: Jul 1, 2025
10:29
Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
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Structural Relationships to Efficacy for Prazole-Derived Antivirals
David A Nyenhuis1, Susan Watanabe2, Rebecca Bernstein1
1Biochemistry and Biophysics Center, NHLBI, NIH, 50 South Drive, Bld 50, Rm 3503, Bethesda, MD, 20892, USA.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|March 6, 2024
Summary
New prazole derivatives inhibit viral production by targeting Tsg101. Modifications enhance efficacy against HIV-1 and SARS-CoV-2, with potential for improved drug half-life and specificity.
Area of Science:
- Biochemistry
- Virology
- Medicinal Chemistry
Background:
- Tsg101 is a key host factor in viral budding.
- Prazole derivatives are being explored for antiviral properties.
Purpose of the Study:
- To characterize prazole derivatives targeting Tsg101.
- To evaluate their efficacy in inhibiting viral particle production.
- To explore structure-activity relationships for enhanced antiviral effects.
Main Methods:
- In vitro characterization of prazole derivatives.
- Assays for viral particle production inhibition.
- Analysis of Tsg101 adduct formation.
- Structure-activity relationship studies.
Main Results:
- Prazoles covalently bind to Tsg101's C73 site.
- Increased steric bulk enhances inhibition of HIV-1 virus-like particle production.
- Novel secondary Tsg101 adducts were formed, suggesting increased half-life and specificity.
- Sulfide derivatives showed effective viral inhibition, targeting SARS-CoV-2.
Conclusions:
- Prazole derivatives are promising antiviral agents targeting Tsg101.
- Structural modifications can optimize antiviral activity and reduce toxicity.
- Further development of these compounds could lead to new antiviral therapies.
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