Figure 1.

Severe Acute Respiratory Syndrome (SARS)-CoV-2 Zoonosis and Cell Entry.

Bat SARS-related CoVs (top left) are thought to transmit through intermediate host(s), with a select subset of viruses having features necessary to infect the human respiratory tract (top right). Infection (lower panel) requires SARS-CoV-2 spike (S) engagement with host angiotensin converting enzyme 2 (ACE2) receptors. Subsequently, surface proteases cleave S2, the fusion-mediating subunit of S, which triggers a series of conformational changes that result in fusion between the viral envelope and the target cell membrane. Features of SARS-CoV-2 that may facilitate human infection include: (1) S1B receptor-binding motifs (RBMs) (in green) that bind orthologous ACE2 receptors; (2) a S1A domain that may confer additional host interactions; and (3) a furin protease cleavage substrate that may confer heightened sensitivity to host protease cleavages [9]. Antiviral antibodies (lower-left inset) prevent infection by: (a) binding S1B RBMs, blocking receptor access; (b) binding distal to RBMs, sterically interfering; (c) binding S1A, possibly preventing alternative attachment to distinct receptors; and (d) binding S2, arresting membrane fusion. Attractive antiviral compounds include protease inhibitors [10], which deactivate membrane fusion triggering and suppress virus entry. This figure was created using BioRender (https://biorender.com/).