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Identification of SARS-CoV-2 Receptor Binding Inhibitors by In Vitro Screening of Drug Libraries
Alon Ben David1, Eran Diamant1, Eyal Dor1
1Department of Biotechnology, Israel Institute for Biological Chemical and Environmental Sciences, Ness Ziona 7410001, Israel.
Molecules (Basel, Switzerland)
|June 2, 2021
Summary
Researchers screened compound libraries to find inhibitors of SARS-CoV-2 binding to human cells. Heparin sodium, aurintricarboxylic acid, and ellagic acid effectively blocked the virus-receptor interaction, offering potential COVID-19 therapies.
Area of Science:
- Virology
- Drug Discovery
- Biochemistry
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the COVID-19 pandemic.
- Viral entry into host cells is initiated by the binding of the SARS-CoV-2 spike protein's receptor-binding domain (RBD) to human angiotensin-converting enzyme 2 (ACE2).
Purpose of the Study:
- To develop and utilize an in vitro assay for high-throughput screening of compound libraries to identify inhibitors of the RBD-ACE2 interaction.
- To evaluate potential drug candidates for SARS-CoV-2 inhibition through repurposing.
Main Methods:
- Development of an in vitro RBD-ACE2 binding assay.
- High-throughput screening of the LOPAC®1280 and DiscoveryProbe™ compound libraries.
- Confirmation of inhibitor efficacy using plaque reduction assays with a SARS-CoV-2 surrogate virus in Vero E6 cells.
- Molecular docking analysis to predict binding sites.
Main Results:
- Three compounds—heparin sodium, aurintricarboxylic acid (ATA), and ellagic acid—demonstrated effective inhibition of RBD-ACE2 binding, with IC50 values between 0.6 and 5.5 µg/mL.
- Heparin sodium and ATA showed confirmed inhibition efficacy in cell-based assays.
- Molecular docking identified potential binding sites for these inhibitors within the RBD.
Conclusions:
- The developed in vitro assay is effective for identifying SARS-CoV-2 inhibitors.
- Heparin sodium, ATA, and ellagic acid are promising candidates for further investigation as COVID-19 therapeutics.
- The screening system can be applied to broader drug libraries for discovering novel SARS-CoV-2 inhibitors.
