Figure 1.

SARS-CoV(-2) host cell infection, replication (Phase I) and induction of immune response (Phase II). Spike protein (S protein) of SARS-CoV-2 binds to host cell membrane presented ACE2 (cellular receptor); it either enters the endocytic pathway (A) or fuses via TMPRSS2-mediated cleavage of the ACE2-S protein complex directly with the cell membrane (B). Traveling down the endosomal pathway, the maturation of early endosomes (EE), via late endosomes (LE) to early lysosomes (EL), and finally lysosomes, is accompanied by vacuolar acidification (indicated as red area). In late endosomes/lysosomes, the ACE2-S protein complex is cleaved via cathepsin L, resulting in the fusion of the viral and host cell membrane. After release into the cytoplasm, translation of viral RNA into the polyprotein takes place. Afterwards, the polyprotein is cleaved into several active non-structural proteins by the chymotrypsin-like protease subunit (3CLpro), including RNA depending RNA polymerase (RdRp). RdRp subsequently synthesizes progeny genomes and subgenomic mRNAs translated to structural proteins at the endoplasmatic reticulum. Both structural proteins and progeny genomes meet in the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), resulting in the assembled SARS-CoV-2 virus. Finally, the nucleocapsid is released from host cell via exocytosis. In Phase II, SARS-CoV-2 is recognized and internalized by antigen presenting cells (APC), triggering an innate immune response which is accompanied by a release of cytokines, including Interleukin-6 (IL-6). In severe cases, a massive release of IL-6 leads to the cytokine release syndrome (CRS).