SARS-CoV-2 virion and host cell membrane

The SARS-CoV-2 virion and host cell membrane interface is the primary site for viral attachment and entry into human cells. This target complex consists of the viral lipid envelope, which houses the Spike (S) protein, and the host cell's plasma or endosomal membrane, which contains the Angiotensin-Converting Enzyme 2 (ACE2) receptor and activating proteases like TMPRSS2 (Hoffmann et al., 2020). The interaction between these two membranes is a multi-step process involving Spike protein binding to ACE2, followed by proteolytic cleavage that triggers the fusion of the viral and cellular bilayers (Walls et al., 2020). This fusion event is essential for the release of the viral RNA genome into the host cytoplasm to initiate replication. Therapeutic agents such as Umifenovir (Arbidol) and the pan-coronavirus fusion inhibitor peptide EK1 target this interface by disrupting the lipid dynamics or blocking the conformational transitions of the Spike protein required for membrane merging (Xia et al., 2020). Because this target represents a physical interface of multiple components rather than a single molecule, it poses unique challenges for drug specificity and the avoidance of host cell membrane toxicity.

Other names

SARS-CoV-2 viral envelope and host cell plasma membraneViral-host membrane fusion interfaceSARS-CoV-2 entry siteSARS-CoV-2 fusion complex

Inhibition of viral-host membrane fusion and prevention of viral genome entry into the host cytoplasm.