SARS-CoV-2 viral entry process

The SARS-CoV-2 viral entry process is the essential mechanism by which the virus identifies, attaches to, and enters host cells to initiate infection. This process is primarily mediated by the interaction between the viral Spike (S) protein and the host cell surface receptor Angiotensin-converting enzyme 2 (ACE2) (Hoffmann et al., 2020, Cell). Following binding, the Spike protein must be 'primed' by host proteases such as Transmembrane serine protease 2 (TMPRSS2) or cathepsin L to facilitate the fusion of the viral envelope with the host cell membrane (Jackson et al., 2022, Nature Reviews Molecular Cell Biology). Because this step is the first stage of the viral life cycle, it is a primary target for neutralizing antibodies and small-molecule inhibitors designed to prevent COVID-19 (V'kovski et al., 2021, Nature Reviews Microbiology). Therapeutic strategies often focus on blocking the Receptor Binding Domain (RBD) of the Spike protein or inhibiting the host proteases required for activation. However, the rapid evolution of the virus leads to mutations in the Spike protein that can reduce the binding affinity of existing drugs and facilitate immune evasion (Harvey et al., 2021, Nature Reviews Microbiology). This process can occur via direct surface fusion or through an endosomal pathway depending on the availability of specific host proteases (Lan et al., 2020, Nature). Understanding the structural transitions of the Spike protein during entry is crucial for developing broad-spectrum antivirals that remain effective against emerging variants.

Other names

SARS-CoV-2 cell entrySpike-mediated entrySARS-CoV-2 infection pathwayCoronavirus entry mechanism

Neutralization of the viral spike protein to prevent ACE2 binding, inhibition of host cell proteases like TMPRSS2 to prevent spike priming, and inhibition of viral-host membrane fusion.