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

Li Yang1, Rong-juan Pei2, Heng Li1,3, Xin-na Ma4, Yu Zhou1, Feng-hua Zhu1, Pei-lan He1, Wei Tang1, Ye-cheng Zhang2, Jin Xiong2, Shu-qi Xiao2, Xian-kun Tong1, Bo Zhang2, Jian-ping Zuo1,3,4
1 Laboratory of Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
2 Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
3 University of Chinese Academy of Sciences, Beijing 100049, China
4 Laboratory of Immunology and Virology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Correspondence to: Xian-kun Tong:, Bo Zhang:, Jian-ping Zuo:,
DOI: 10.1038/s41401-020-00556-6
Received: 7 August 2020
Accepted: 9 October 2020
Advance online: 28 October 2020


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.
Keywords: COVID-19; SARS-CoV-2; virus entry inhibitors; high throughput screening assay; approved drug library; histamine receptor antagonists; clemastine

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