Identification of SARS-CoV-2 entry inhibitors among already approved drugs

To discover effective drugs for COVID-19 treatment amongst already clinically approved drugs, we developed a high throughput screening assay for SARS-CoV-2 virus entry inhibitors using SARS2-S pseudotyped virus. An approved drug library of 1800 small molecular drugs was screened for SARS2 entry inhibitors and 15 active drugs were identified as specific SARS2-S pseudovirus entry inhibitors. Antiviral tests using native SARS-CoV-2 virus in Vero E6 cells confirmed that 7 of these drugs (clemastine, amiodarone, trimeprazine, bosutinib, toremifene, flupenthixol, and azelastine) significantly inhibited SARS2 replication, reducing supernatant viral RNA load with a promising level of activity. Three of the drugs were classified as histamine receptor antagonists with clemastine showing the strongest anti-SARS2 activity (EC50 = 0.95 +/- 0.83 mu M). Our work suggests that these 7 drugs could enter into further in vivo studies and clinical investigations for COVID-19 treatment.

Automated summary

A high throughput screening assay was developed to identify entry inhibitors for SARS-CoV-2 virus, leading to the discovery of 15 active drugs with specific antiviral properties. Seven of these drugs showed promising levels of activity in inhibiting SARS2 replication in Vero E6 cells, suggesting their potential for further in vivo studies and clinical investigations for COVID-19 treatment.