Fig. 1

Pulmonary epithelium and cell penetration pathways of SARS-CoV-2. A One of the important ports of virus entry is respiratory epithelial cells. Upper airways are lined with pseudostratified epithelium. In distal airways, height of the epithelium decreases and eventually becomes squamous in the alveoli. It consists mainly of ciliated cells as well as goblet cells, Clara/club cells, basal cells, and neuroendocrine cells. Ciliated cells have hair-like projections, which help move up mucus that rests on them. Goblet cells produce and secrete mucin. Club cells secret specific proteins and surfactant protein (SP)-A, SP-B, and SP-D. Alveolar type 1 and 2 cells are involved in gas exchange and the generation of SPs, respectively. Stem cells in this epithelium include basal cells, “variant” club cells, neuroendocrine cells, and cell population in bronchoalveolar duct junctions. B SARS‐CoV‐2 entry into the host cells occurs via direct membrane fusion (1) and endocytosis (2). In both pathways, spike (S) protein must bind to host cell receptors such as ACE2, NRP1, CLR, MGL, L-SIGN, DC-SIGN, TLRs, and GRP78. In endocytosis-mediated entry, following binding to cell receptor, virus entry into the host cell occurs and the S protein is activated in endosomes by furin cleavage. Fusion occurs by cathepsin-L action, and virus genetic material is released into cytosol, entering the virus through direct fusion mediated by proteases such as TMPRSS2 and/or furin. S protein interacts with a host cell receptor and becomes activated. Eventually, the membranes are merged and the virus releases its genetic material (RNA) via the formed pore into the cytosol. SARS-CoV-2 RNA is replicated and transcribed by host organelles such as ribosomes, Golgi apparatus, rough endoplasmic reticulum (rER), etc. Finally, the virus spreads to other cells and tissues. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; NRP1, neuropilin-1; ACE2, angiotensin-converting enzyme 2; MGL, macrophage galactose-type lectin; CLR, C-lectin type receptors; L-SIGN, homolog dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin related; DC-SIGN, dendritic cell-specific intracellular adhesion molecule-3-grabbing non-integrin; TLRs, Toll-like receptors; GRP78, non-immune receptor glucose-regulated protein 78; TMPRSS2, transmembrane protease, serine 2