Abstract
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 (EC 50 = 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.
Keywords: COVID-19; SARS-CoV-2; approved drug library; clemastine; high throughput screening assay; histamine receptor antagonists; virus entry inhibitors.
【저자키워드】 COVID-19, SARS-CoV-2, approved drug library, clemastine, high throughput screening assay, histamine receptor antagonists, virus entry inhibitors., 【초록키워드】 Treatment, SARS-CoV-2 virus, drug, inhibitors, approved drugs, clemastine, effective drugs, Replication, COVID-19 treatment, Viral, Pseudotyped virus, virus entry, VERO E6 cells, receptor, SARS2, molecular, Vero E6 cell, in vivo, viral RNA load, Amiodarone, Entry inhibitor, pseudovirus entry, Histamine, Vero E6, azelastine, histamine receptor, trimeprazine, bosutinib, toremifene, clinical investigation, drug library, flupenthixol, supernatant, antagonist, significantly, clinically, inhibited, approved, screened, reducing, effective drug, 【제목키워드】 inhibitor, identification, approved drug, SARS-CoV-2 entry,