Journal
ACTA PHARMACOLOGICA SINICA
Volume 42, Issue 8, Pages 1347-1353Publisher
NATURE PUBL GROUP
DOI: 10.1038/s41401-020-00556-6
Keywords
COVID-19; SARS-CoV-2; virus entry inhibitors; high throughput screening assay; approved drug library; histamine receptor antagonists; clemastine
Funding
- National Key Research and Development Program of China [2018YFC1200604]
Ask authors/readers for more resources
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.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available