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Assays for the Identification of Novel Antivirals against Bluetongue Virus
Published on: October 11, 2013
FDA-approved drug repurposing screen identifies inhibitors of SARS-CoV-2 pseudovirus entry
Manisha Singh1, Shruthi Shanmukha2, Raghda E Eldesouki3
1Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States.
Background And Purpose:
The coronavirus disease 2019 (COVID-19) pandemic has devastated global health and the economy, underscoring the urgent need for extensive research into the mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry and the development of effective therapeutic interventions.
Experimental Approach:
We established a cell line expressing human angiotensin-converting enzyme 2 (ACE2). We used it as a model of pseudotyped viral entry using murine leukemia virus (MLV) expressing SARS-CoV-2 spike (S) protein on its surface and firefly luciferase as a reporter. We screened an U.S. Food and Drug Administration (FDA)-approved compound library for inhibiting ACE2-dependent SARS-CoV-2 pseudotyped viral entry and identified several drug-repurposing candidates.
Key Results:
We identified 18 drugs and drug candidates, including 14 previously reported inhibitors of viral entry and four novel candidates. Pyridoxal 5'-phosphate, Dovitinib, Adefovir dipivoxil, and Biapenem potently inhibit ACE2-dependent viral entry with inhibitory concentration 50% (IC50) values of 57nM, 74 nM, 130 nM, and 183 nM, respectively.
Conclusion And Implications:
We identified four novel FDA-approved candidate drugs for anti-SARS-CoV-2 combination therapy. Our findings contribute to the growing body of evidence supporting drug repurposing as a viable strategy for rapidly developing COVID-19 treatments.
Insights
Researchers screened FDA-approved drugs to find new COVID-19 treatments. Four novel drug candidates were identified that inhibit SARS-CoV-2 viral entry, offering a promising strategy for combination therapy.
Area of Science:
- Virology
- Drug Discovery
- Molecular Biology
Background:
- The COVID-19 pandemic necessitates urgent research into SARS-CoV-2 mechanisms and treatments.
- Understanding viral entry pathways is crucial for developing effective therapeutic interventions.
Purpose of the Study:
- To identify FDA-approved drugs that can inhibit SARS-CoV-2 entry into host cells.
- To explore drug repurposing as a rapid strategy for COVID-19 treatment development.
Main Methods:
- Established a cell line expressing human ACE2 as a model for SARS-CoV-2 entry.
- Utilized pseudotyped viral entry assays with MLV displaying SARS-CoV-2 spike protein.
- Screened an FDA-approved compound library for inhibitors of ACE2-dependent viral entry.
Main Results:
- Identified 18 drug candidates inhibiting viral entry, including 4 novel compounds.
- Pyridoxal 5'-phosphate, Dovitinib, Adefovir dipivoxil, and Biapenem showed potent inhibition (IC50 values < 200 nM).
- These drugs target the ACE2-dependent entry mechanism of SARS-CoV-2.
Conclusions:
- Identified four novel FDA-approved drug candidates for potential anti-SARS-CoV-2 combination therapy.
- Drug repurposing is a viable and rapid strategy for developing COVID-19 treatments.
- Findings support further investigation of these candidates for clinical application.
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