Direct derivation of human alveolospheres for SARS-CoV-2 infection modeling and drug screening.
Cell Rep
; 35(10): 109218, 2021 06 08.
Article
in En
| MEDLINE
| ID: mdl-34038715
ABSTRACT
Although the main cellular target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is thought to be alveolar cells, the absence of their tractable culture system precludes the development of a clinically relevant SARS-CoV-2 infection model. Here, we establish an efficient human alveolosphere culture method and sphere-based drug testing platform for SARS-CoV-2. Alveolospheres exhibit indolent growth in a Wnt- and R-spondin-dependent manner. Gene expression, immunofluorescence, and electron microscopy analyses reveal the presence of alveolar cells in alveolospheres. Alveolospheres express ACE2 and allow SARS-CoV-2 to propagate nearly 100,000-fold in 3 days of infection. Whereas lopinavir and nelfinavir, protease inhibitors used for the treatment of human immunodeficiency virus (HIV) infection, have a modest anti-viral effect on SARS-CoV-2, remdesivir, a nucleotide prodrug, shows an anti-viral effect at the concentration comparable with the circulating drug level. These results demonstrate the validity of the alveolosphere culture system for the development of therapeutic agents to combat SARS-CoV-2.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Drug Evaluation, Preclinical
/
Alveolar Epithelial Cells
/
SARS-CoV-2
/
COVID-19 Drug Treatment
Type of study:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Limits:
Humans
Language:
En
Journal:
Cell Rep
Year:
2021
Type:
Article
Affiliation country:
Japan