FIG 5.

Fusion and entry mechanisms of SARS-CoV-2. SARS-CoV-2 enters the host cell via two different pathways: TMPRSS2-mediated cytoplasm membrane fusion and cathepsin-mediated endosomal membrane fusion. Peptide-based pan-CoV fusion inhibitors can inhibit both fusion pathways, while the inhibitors targeting TMPRSS2 and cathepsin L are expected to inhibit the cytoplasm and endosomal membrane fusion pathways, respectively. Chloroquine and hydroxychloroquine as agents targeting the endosomal acidification can inhibit SARS-CoV-2 S protein-mediated endosomal membrane fusion. Infection with the Omicron variant is not blocked by TMPRSS2 inhibitor (Camstat or Nafamostat) but is instead largely mediated via the endocytic pathway.