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).