Identification of SARS-CoV-2 entry inhibitors among already approved drugs #MMPMID33116249
Yang L; Pei RJ; Li H; Ma XN; Zhou Y; Zhu FH; He PL; Tang W; Zhang YC; Xiong J; Xiao SQ; Tong XK; Zhang B; Zuo JP
Acta Pharmacol Sin 2021[Aug]; 42 (8): 1347-1353 PMID33116249show ga
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 microM). Our work suggests that these 7 drugs could enter into further in vivo studies and clinical investigations for COVID-19 treatment.
free
free
free
Acta+Pharmacol+Sin 2021 ; 42 (8): 1347-1353
