FDA-approved drug repurposing screen identifies inhibitors of SARS-CoV-2 pseudovirus entry

Manisha Singh ¹ Shruthi Shanmukha ² Raghda Eldesouki ³ Maged M. Harraz ^1*

• ¹ Neurology, School of Medicine, University of Maryland, Baltimore, MD, United States
• ² School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States
• ³ Faculty of Medicine, Suez Canal University, Ismaïlia, Ismailia, Egypt

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. Conclusions & 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.