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Updated: Aug 15, 2025
Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Identification of Polyphenol Derivatives as Novel SARS-CoV-2 and DENV Non-Nucleoside RdRp Inhibitors
Shenghua Gao1,2,3, Letian Song1,2, Hongtao Xu4
1Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
Two novel polyphenol derivatives, DF-47 and DF-51, show potential as broad-spectrum inhibitors of viral RNA-dependent RNA polymerase (RdRp). These compounds effectively target both SARS-CoV-2 and Dengue virus polymerases, offering a new therapeutic avenue.
Area of Science:
- Virology
- Medicinal Chemistry
- Drug Discovery
Background:
- Coronavirus Disease 2019 (COVID-19) and dengue fever (DF) represent ongoing global public health challenges.
- Effective antiviral therapies are crucial for managing these infectious diseases.
Purpose of the Study:
- To identify novel inhibitors targeting the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 and Dengue virus (DENV).
- To explore the potential of piperazine-based polyphenol derivatives as broad-spectrum antiviral agents.
Main Methods:
- Screening of an in-house library for RdRp inhibitors.
- In vitro antiviral assays against SARS-CoV-2 and DENV.
- In silico molecular simulations to analyze binding modes with viral RdRp.
Main Results:
- Two compounds, DF-47 and DF-51, were identified as potent inhibitors of both SARS-CoV-2 and DENV RdRp.
- In silico analysis revealed stable binding interactions, including Mg2+ chelation near the polymerase active site.
- DF-47 and DF-51 demonstrated effective inhibition of viral polymerase activity.
Conclusions:
- Piperazine-based polyphenols DF-47 and DF-51 exhibit significant inhibitory effects on distinct viral RdRp enzymes.
- These compounds represent a promising new scaffold for developing broad-spectrum, non-nucleoside RdRp inhibitors.
- Further development of DF-47 and DF-51 could lead to novel treatments for both COVID-19 and dengue fever.
