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Updated: Oct 8, 2025
High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
Published on: May 5, 2014
High-Throughput Screening and Identification of Human Adenovirus Type 5 Inhibitors
Xiaojing Wen1,2,3, Li Zhang1, Shan Zhao4
1Division of Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC) and World Health Organization (WHO) Collaborating Center for Standardization and Evaluation of Biologicals, Beijing, China.
Abstract:
Human adenovirus infections can develop into diffuse multi-organ diseases in young children and immunocompromised patients, and severe cases can lead to death. However, there are no approved antiviral drugs available to treat adenovirus diseases. In this study, a chemiluminescence-based, high-throughput screening (HTS) assay was developed and applied to screen human adenovirus 5(HAdV5)inhibitors from 1,813 approved drug library and 556 traditional Chinese medicine-sourced small-molecule compounds. We identified three compounds with in vitro anti-HAdV5 activities in the low-micromolar range (EC50 values 0.3-4.5 μM, selectivity index values 20-300) that also showed inhibitory effects on HAdV3. Cardamomin (CDM) had good anti-HAdV5 activity in vitro. Furthermore, three dilutions of CDM (150, 75, and 37.5 mg/kg/d) administered to BALB/c mouse models inhibited HAdV5-fluc infection at 1 day post-infection by 80% (p < 0.05), 76% (p < 0.05), and 58% (p < 0.05), respectively. HE-staining of pathological tissue sections of mice infected with a wildtype adenoviral strain showed that CDM had a protective effect on tissues, especially in the liver, and greatly inhibited virus-induced necrosis of liver tissue. Thus, CDM inhibits adenovirus replication in vivo and in vitro. This study established a high-throughput screening method for anti-HAdV5 drugs and demonstrated CDM to be a candidate for HAdV5 therapy, potentially providing a new treatment for patients infected with adenoviruses.
Insights
Researchers developed a high-throughput screening method to find new adenovirus treatments. Cardamomin (CDM) showed significant antiviral activity against human adenovirus 5 (HAdV5) in vitro and in vivo, offering a potential new therapy.
Area of Science:
- Virology
- Drug Discovery
- Immunology
Background:
- Human adenovirus infections pose serious health risks, particularly in vulnerable populations.
- Currently, no approved antiviral drugs exist to treat adenovirus diseases.
- Effective therapeutic strategies for adenovirus infections are urgently needed.
Purpose of the Study:
- To develop a high-throughput screening (HTS) assay for identifying human adenovirus 5 (HAdV5) inhibitors.
- To screen approved drug libraries and traditional Chinese medicine compounds for anti-HAdV5 activity.
- To evaluate the therapeutic potential of identified compounds, including Cardamomin (CDM), against HAdV5 infection.
Main Methods:
- Developed a chemiluminescence-based HTS assay.
- Screened 1,813 approved drugs and 556 traditional Chinese medicine compounds.
- Tested lead compounds in vitro and in vivo using HAdV5 infection models in mice.
Main Results:
- Identified three compounds with in vitro anti-HAdV5 activity (EC50: 0.3-4.5 μM, SI: 20-300), also effective against HAdV3.
- Cardamomin (CDM) demonstrated potent in vitro anti-HAdV5 activity.
- CDM administration in mice significantly inhibited HAdV5-fluc infection and protected liver tissue from viral necrosis.
Conclusions:
- CDM effectively inhibits HAdV5 replication both in vitro and in vivo.
- The developed HTS assay is a valuable tool for discovering novel anti-adenovirus drugs.
- CDM is a promising candidate for developing new HAdV5 therapies.
