SARS-CoV-2 and the NLRP3 inflammasome

Inflammasomes are endogenous sensors of viral infection activated by damage associated molecular patterns (DAMPs) and pathogen associated molecular patterns (PAMPs). Once activated by DAMPs or PAMPs, inflammasomes assemble and catalyze the autoactivation of Caspase-1 and subsequent maturation of proinflammatory cytokines. Although these multiprotein systems are key to innate immunity, the overactivity of inflammasomes can perpetuate a hyperactive immune response causing damaging inflammation. In COVID-19, devastating inflammation contributes substantially to morbidity and mortality. Patients with severe COVID-19 exhibit high levels of IL-1B and IL-18 indicating robust activity of the NLRP3 inflammasome. The mechanisms by which SARS-CoV-2 incites the NLRP3 inflammasome have not been extensively characterized, but may be inferred from those of its close relative SARS-CoV. Several proteins from the SARS coronaviruses and other coronaviruses have been found to preferentially incite the NLRP3 inflammasome, both by direct association with inflammasome components and indirect disruption of ion gradients. Here we present our curation of these mechanisms and the possible targets in the NLRP3 inflammasome system for COVID-19 therapeutics.