Drug repurposing screens reveal cell-type-specific entry pathways and FDA-approved drugs active against SARS-Cov-2.
Cell Rep
; 35(1): 108959, 2021 04 06.
Article
in English
| MEDLINE | ID: covidwho-1163484
ABSTRACT
There is an urgent need for antivirals to treat the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To identify new candidates, we screen a repurposing library of â¼3,000 drugs. Screening in Vero cells finds few antivirals, while screening in human Huh7.5 cells validates 23 diverse antiviral drugs. Extending our studies to lung epithelial cells, we find that there are major differences in drug sensitivity and entry pathways used by SARS-CoV-2 in these cells. Entry in lung epithelial Calu-3 cells is pH independent and requires TMPRSS2, while entry in Vero and Huh7.5 cells requires low pH and triggering by acid-dependent endosomal proteases. Moreover, we find nine drugs are antiviral in respiratory cells, seven of which have been used in humans, and three are US Food and Drug Administration (FDA) approved, including cyclosporine. We find that the antiviral activity of cyclosporine is targeting Cyclophilin rather than calcineurin, revealing essential host targets that have the potential for rapid clinical implementation.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Cyclosporine
/
Epithelial Cells
/
Drug Repositioning
/
SARS-CoV-2
/
COVID-19 Drug Treatment
/
Lung
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Country/Region as subject:
North America
Language:
English
Journal:
Cell Rep
Year:
2021
Document Type:
Article
Affiliation country:
J.celrep.2021.108959
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