ICU patients with severe COVID-19 had higher plasma levels of IL-1β/2/6/7/10, TNFα, CSF3, CCL3, CCL3, and CXC10, suggesting that these excessive inflammatory responses are related to disease severity.49 To further evaluate whether compounds 14a and 14b could exert anti-inflammatory activity by dually inhibiting CTSL and CAPN1, we determined the potential anti-inflammatory effect of 14a and 14b by measuring their capacity to suppress lipopolysaccharide (LPS)-induced expression of proinflammatory cytokines (IL-1β, IL-6) and chemokines (CCL3, CXCL10). Here, TNF is linked to COVID-19.