Interferons
Interferons (IFNs) are under investigation for the treatment of COVID-19, mainly in combination with lopinavir/ritonavir (Chinese Clinical Trial Registry identifier: ChiCTR2000029387) or lopinavir/ritonavir/ribavirin (NCT04276688 and EudraCT database identifier: 2020-001023-14).
Selective interactions between type I-IFNs and NLRP3 inflammasome have been documented in the literature. For instance, both type-I IFNs and IFN-γ evoke higher expression of inducible nitric oxide (NO) synthase, increasing levels of endogenous NO, which inhibits NLRP3 oligomerization by means of direct S-nitrosylation of the NLRP3 protein, avoiding full inflammasome organization (Mishra et al., 2013). Another mechanism resides in the ability of type-I IFN to decrease the NLRP3 inflammasome activation via the signal transducer and activator of transcription 1 (STAT1) that induces caspase-1 to process the IL-1β precursor (Kopitar-Jerala, 2017).