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

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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 μM).Our work suggests that these 7 drugs could enter into further in vivo studies and clinical investigations for COVID-19 treatment.
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