SARS-CoV-2 Virus-Host Interaction Antibody Sampler Kit

Background

The cause of the COVID-19 pandemic is a novel and highly pathogenic coronavirus, termed SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2). SARS-CoV-2 is a member of the Coronaviridae family of viruses (1). The SARS-CoV-2 virion is comprised of four key structural proteins: spike (S), envelope (E), membrane (M), and nucleocapsid (N) (2). Coronavirus spike proteins are class I fusion proteins and harbor an ectodomain, a transmembrane domain, and an intracellular tail (3,4). The highly glycosylated ectodomain projects from the viral envelope surface and facilitates attachment and fusion with the host cell membrane. The ectodomain can be further subdivided into the receptor-binding domain (RBD) S1 and membrane-fusion (S2) subunits, which are produced upon proteolysis by host proteases. S1 and S2 subunits are reassociated after cleavage, assembling into crown-like homotrimers (2,4).

The SARS-CoV-2 spike protein contains a novel tetrabasic "furin cleavage site" (FCS) at the S1/S2 junction. Research studies suggest this site is cleaved by proprotein convertases (e.g., furin) or lysosomal proteases (e.g., cathepsin L) (5,6). S1/S2 cleavage elicits a confirmational change in the spike protein that positions elements of the trimeric RBD in an exposed "up" position, priming it for interaction with host receptor proteins. Cleavage can occur at multiple steps of the viral lifecycle, including during viral packaging, or upon contact of the intact virion with the host cell surface. This novel cleavage event has been suggested to contribute to the high infectivity rate of the SARS-CoV-2 virus (7).

The SARS-CoV-2 virus has been shown to utilize the angiotensin-converting enzyme 2 (ACE2) protein as its primary receptor for cellular entry (8). However, research studies have suggested that other cell surface proteins may serve as receptors or co-receptors for SARS-CoV-2. These include neuropilin-1 (NPN1), a single-pass transmembrane receptor that can function as part of a semaphorin receptor complex, and as a vascular endothelial growth factor (VEGF) receptor (9), and Basigin/EMMPRIN (CD147), a type I integral membrane receptor belonging to the immunoglobulin superfamily (10).