SARS-CoV-2 entry and attachment

SARS-CoV-2 entry and attachment refers to the multi-step biological process by which the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recognizes and penetrates host cells. This process is primarily initiated by the interaction between the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein and the host cell surface receptor, Angiotensin-converting enzyme 2 (ACE2). Following attachment, the Spike protein must be proteolytically activated (primed) by host enzymes, such as the transmembrane protease serine 2 (TMPRSS2) at the plasma membrane or cathepsin L within endosomes, to trigger a conformational change that facilitates membrane fusion and the release of the viral genome into the host cytoplasm. Other host factors, including Neuropilin-1, CD147, and heparan sulfate proteoglycans, act as co-receptors or attachment factors that enhance viral entry efficiency. Because this step is essential for the initiation of infection, it is a primary focus for therapeutic development, including neutralizing monoclonal antibodies that block the Spike-ACE2 interface and small molecule inhibitors targeting host proteases or the fusion process itself.

Other names

SARS-CoV-2 viral entrySARS-CoV-2 attachmentCOVID-19 entry pathwaySARS-CoV-2 entry mechanism

The process is targeted through multiple mechanisms: neutralization of the viral Spike protein to prevent binding to the host ACE2 receptor; inhibition of host cell surface proteases like TMPRSS2 or endosomal proteases like Cathepsin L to prevent Spike protein priming; and inhibition of endosomal acidification to block viral-host membrane fusion.