Antiviral agents
The administration of the protease inhibitor ritonavir in association with lopinavir, has been tested for the treatment of SARS-CoV-2 infection and COVID-19 pneumonia (Cao et al., 2020) and there are several on-going clinical trials in China (NCT04255017, NCT04261907, NCT04286503, NCT04295551), Hong Kong (NCT04276688), Republic of Korea (NCT04307693) and in Europe (NCT04315948, NCT04328285). The protease inhibitor darunavir is under investigation as an alternative drug to lopinavir/ritonavir treatment in COVID-19 (NCT04252274 and ChiCTR2000029541). Other two clinical trials (NCT04261270 and NCT04303299) have been proposed to evaluate oseltamivir, a neuraminidase inhibitor approved for the treatment of influenza, alone or in combination with ritonavir or favipiravir, darunavir and chloroquine. Interestingly, the three antiviral drugs here mentioned interfere with NLRP3 inflammasome activation. Ritonavir has been demonstrated to inhibit caspase-1 activation leading to reduced cleavage of pro-IL-18 (Lopez-Castejon & Pelegrin, 2012), whereas darunavir limits the expression of key regulators of NLRP3 inflammasome complex formation, TLR4 and NF-κB (Zhang et al., 2018). The interaction of oseltamivir with NLRP3 inflammasome has been demonstrated in an in vivo study on influenza A pdm09 virus infection (Jia et al., 2018).