Severe acute respiratory syndrome coronavirus 2 entry machinery (SARS-CoV-2 entry machinery) (None)

The SARS-CoV-2 entry machinery is the complex of viral and host proteins required for the virus to infect human cells, primarily consisting of the viral Spike (S) protein and the host cell receptors Angiotensin-converting enzyme 2 (ACE2) and Transmembrane serine protease 2 (TMPRSS2) (Hoffmann et al., 2020, Cell). The process begins when the S protein's receptor-binding domain (RBD) attaches to ACE2, a step often facilitated by initial docking on Heparan sulfate proteoglycans (HSPGs) (Clausen et al., 2020, Cell). Following attachment, TMPRSS2 cleaves the S protein at the S1/S2 site, triggering a conformational change that allows the virus to fuse with the host cell membrane (Shang et al., 2020, Nature). Therapeutic strategies like lactoferrin-coated zinc nanoparticles aim to disrupt this machinery; lactoferrin binds to HSPGs to block viral docking, while zinc ions may inhibit viral replication or stabilize host membranes (Campione et al., 2020, Int J Mol Sci; Skalny et al., 2020, Nutrients). This machinery is the primary target for most COVID-19 vaccines and monoclonal antibodies, which work by neutralizing the Spike protein to prevent viral entry (Kyriakidis et al., 2021, NPJ Vaccines). Because this machinery is essential for infection, it remains a high-priority target for developing broad-spectrum antivirals against emerging variants.

Other names

SARS-CoV-2 Spike-ACE2 complexSpike-ACE2-TMPRSS2 axisViral entry pathwaySARS-CoV-2 entry pathway

Inhibition of viral attachment to host cell receptors and prevention of membrane fusion.