Evaluation of SARS-CoV-2 entry, inflammation and new therapeutics in human lung tissue cells.
PLoS Pathog
; 18(1): e1010171, 2022 01.
Article
in English
| MEDLINE | ID: covidwho-2327858
ABSTRACT
The development of physiological models that reproduce SARS-CoV-2 infection in primary human cells will be instrumental to identify host-pathogen interactions and potential therapeutics. Here, using cell suspensions directly from primary human lung tissues (HLT), we have developed a rapid platform for the identification of viral targets and the expression of viral entry factors, as well as for the screening of viral entry inhibitors and anti-inflammatory compounds. The direct use of HLT cells, without long-term cell culture and in vitro differentiation approaches, preserves main immune and structural cell populations, including the most susceptible cell targets for SARS-CoV-2; alveolar type II (AT-II) cells, while maintaining the expression of proteins involved in viral infection, such as ACE2, TMPRSS2, CD147 and AXL. Further, antiviral testing of 39 drug candidates reveals a highly reproducible method, suitable for different SARS-CoV-2 variants, and provides the identification of new compounds missed by conventional systems, such as VeroE6. Using this method, we also show that interferons do not modulate ACE2 expression, and that stimulation of local inflammatory responses can be modulated by different compounds with antiviral activity. Overall, we present a relevant and rapid method for the study of SARS-CoV-2.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Virus Internalization
/
SARS-CoV-2
/
COVID-19 Drug Treatment
/
Lung
Type of study:
Experimental Studies
/
Prognostic study
Topics:
Traditional medicine
/
Variants
Limits:
Adult
/
Animals
/
Humans
Language:
English
Journal:
PLoS Pathog
Year:
2022
Document Type:
Article
Affiliation country:
Journal.ppat.1010171
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