Identification of immunomodulatory drugs that inhibit multiple inflammasomes and impair SARS-CoV-2 infection.
Sci Adv
; 8(37): eabo5400, 2022 09 16.
Article
in English
| MEDLINE | ID: covidwho-2029457
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces mild or asymptomatic COVID-19 in most cases, but some patients develop an excessive inflammatory process that can be fatal. As the NLRP3 inflammasome and additional inflammasomes are implicated in disease aggravation, drug repositioning to target inflammasomes emerges as a strategy to treat COVID-19. Here, we performed a high-throughput screening using a 2560 small-molecule compound library and identified FDA-approved drugs that function as pan-inflammasome inhibitors. Our best hit, niclosamide (NIC), effectively inhibits both inflammasome activation and SARS-CoV-2 replication. Mechanistically, induction of autophagy by NIC partially accounts for inhibition of NLRP3 and AIM2 inflammasomes, but NIC-mediated inhibition of NAIP/NLRC4 inflammasome are autophagy independent. NIC potently inhibited inflammasome activation in human monocytes infected in vitro, in PBMCs from patients with COVID-19, and in vivo in a mouse model of SARS-CoV-2 infection. This study provides relevant information regarding the immunomodulatory functions of this promising drug for COVID-19 treatment.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Inflammasomes
/
COVID-19 Drug Treatment
Limits:
Animals
/
Humans
Language:
English
Journal:
Sci Adv
Year:
2022
Document Type:
Article
Affiliation country:
Sciadv.abo5400
Similar
MEDLINE
...
LILACS
LIS