In Vitro Models for Studying Entry, Tissue Tropism, and Therapeutic Approaches of Highly Pathogenic Coronaviruses

Figure 1

Coronaviruses (CoVs) are enveloped nonsegmented positive-sense RNA viruses belonging to the family Coronaviridae. Four genera are known: alpha-, beta-, gamma-, and delta-CoVs. Beta-CoVs are accountable for zoonotic outbreaks as severe acute respiratory syndromes- (SARS-) CoV, Middle East respiratory syndrome virus- (MERS-) CoV, and now, the novel SARS-like coronavirus (SARS-CoV-2). CoVs encode several nonstructural and structural proteins as genome-associated nucleocapsid protein (N), envelope protein (E), and spike (S) glycoprotein. In particular, S protein is crucial for viral attachment, fusion, and entry into epithelial cells. SARS-CoV and SARS-CoV-2 bind to ACE2 receptor highly expressed on ciliated epithelial cells, whereas MERS-CoV enters nonciliated epithelial cells binding the CD26/DPP4 receptor. Several host cellular proteases are needed to activate the S protein (e.g., TMPRSS2, furin, and cathepsins) and viral entry into cells.