Fig. 3

SARS-CoV-2 induces inflammatory dysfunction through over-stimulating NF-κB activation. During invading, SARS-CoV-2 occupies ACE2 and inhibits its activity, which leads to increased ANG II/AT1R and inhibited Ang(1–7)-MasR axis, resulting in enhanced NF-κB activation. During invasion SARS-CoV-2 could be recognized by TLR4. After invasion, uncoated virus single strand RNA could be recognized by TLR7/8. During RNA replication the double strand RNA could be recognized by TLR3. Some anti-virus drugs inhibit the invasion SARS-CoV-2 replication, such as remdesivir, molnupiravir and paxlovid. These TLRs could induce the NF-κB activation which induces the expression of down-stream pro-inflammatory cytokines and chemokines, such as TNFα, IL-1β, IL-6, MCP1 and so on. All of these molecules could further enhance the NF-κB activation through the NF-κB self-activation or other pathways. IL-6/IL-6R monoclonal antibodies or JAK inhibitors suppress NF-κB activation by inhibiting IL-6/JAK/STAT3 signaling, such as tocilizumab, sarilumab, siltuximab, clazakizumab, baricitinib, ruxolitinib and tofacitinib