Figure 1.

The pathological mechanism of SARS-CoV-2 infection of cells. SARS-CoV-2 virions consist of structural proteins, namely spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. The viral S1 protein specifically binds to the cell surface ACE2 receptor and mediates viral uptake and fusion through the cleavage of TMPRSS2 and the endocytosis regulator AP2-associated protein kinase 1 (AAK1). Following entry of the virus into the host cell, viral genomic RNA is released into the cytosol and translated into viral polymerase proteins. Subsequently, subgenomic (-) RNAs are synthesized and used as templates for subgenomic (+) messenger RNAs (mRNAs). The N proteins and viral RNA are replicated, transcribed, and synthesized in the cytoplasm, whereas the other structural proteins (S, M, and E) are transcribed and translated in the endoplasmic reticulum (ER). The resulting structural proteins enter the ER-Golgi intermediate compartment for virion assembly and are released from infected cells through exocytosis. At the same time, the RNA released by the virus is recognized by the pattern recognition receptor TLR7, which promotes the translocation of NF-κB and IRF7 to the nucleus and the expression of pro-inflammatory cytokines, thereby regulating the clearance of the virus by the immune system. In addition, the generated virus particles interact with neuropilin-1 to activate innate immune cells such as macrophages and DCs. It does not only promote the apoptosis of infected cells, but also induces the expression of antiviral cytokines (such as IFN-γ), upregulates the expression of pro-inflammatory cytokines (TNF-α and IL-6) and inflammatory chemokines (CCL3, CCL5, CCL2, and CXCL10), and thus inhibits infection by the virus.