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

  • Acta Pharmacol Sin. 2021 Aug;42(8):1347-1353. doi: 10.1038/s41401-020-00556-6.
Li Yang   #  1 ,  Rong-Juan Pei   #  2 ,  Heng Li   #  1  3 ,  Xin-Na Ma  4 ,  Yu Zhou  1 ,  Feng-Hua Zhu  1 ,  Pei-Lan He  1 ,  Wei Tang  1 ,  Ye-Cheng Zhang  2 ,  Jin Xiong  2 ,  Shu-Qi Xiao  2 ,  Xian-Kun Tong  5 ,  Bo Zhang  6 ,  Jian-Ping Zuo  7  8  9
Affiliations
  • 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.
  • 5. Laboratory of Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. [email protected].
  • 6. Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China. [email protected].
  • 7. Laboratory of Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. [email protected].
  • 8. University of Chinese Academy of Sciences, Beijing, 100049, China. [email protected].
  • 9. Laboratory of Immunology and Virology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. [email protected].
  • # Contributed equally.
PMID: 33116249 DOI: 10.1038/s41401-020-00556-6
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 (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; approved drug library; clemastine; high throughput screening assay; histamine receptor antagonists; virus entry inhibitors.
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