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

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% (IC 50 ) 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.