Seasonal coronavirus infections trigger NLRP3 inflammasome activation in macrophages but is therapeutically targetable.

Publication date: Jul 15, 2023

Seasonal coronaviruses widely circulate in the global population, and severe complications can occur in specific vulnerable populations. Little is known on their pathogenic mechanisms and no approved treatment is available. Here, we present anecdotal evidence that the level of IL-1β, a hallmark of inflammasome activation, appears elevated in a subset of seasonal coronavirus infected patients. We found that cultured human macrophages support the full life cycle of three cultivatable seasonal coronaviruses. Their infections effectively activate NLRP3 inflammasome activation through TLR4 ligation and NF-_705B activation. This activation can be attenuated by specific pharmacological inhibitors and clinically used medications including dexamethasone and flufenamic acid. Interestingly, combination of antiviral and anti-inflammatory drugs simultaneously inhibit seasonal coronavirus-triggered inflammatory response and viral replication. Collectively, these findings show that the TLR4/NF-_705B/NLRP3 axis drives seasonal coronavirus triggered-inflammatory response, which in turn represents a viable therapeutic target.

Concepts Keywords
Coronaviruses Combination treatment
Cultured NLRP3 inflammasome
Global Seasonal coronavirus
Pharmacological Therapeutic targeting
Seasonal

Semantics

Type Source Name
disease VO Optaflu
disease MESH coronavirus infections
disease VO population
disease MESH complications
disease MESH infections
drug DRUGBANK Dexamethasone
drug DRUGBANK Flufenamic Acid
pathway KEGG Viral replication
disease VO viable

Original Article

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