SARS Coronavirus Redux

Abstract

As an atypical pneumonia began to appear in December 2019, Zhou et al. worked with remarkable speed to identify the associated virus, determine its relationship to animal viruses, and evaluate factors conferring infection susceptibility and resistance. These foundational results are being advanced to control the current worldwide human coronavirus epidemic.

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/).