Preventing SARS-CoV-2 infection using Fv-antibodies targeting the proprotein convertase (PPC) cleavage site.

Fv-antibodies targeting the proprotein convertase (PPC) region of the SARS-CoV-2 spike protein (SP) were screened from an Fv-antibody library to inhibit SARS-CoV-2 infection. Two selected Fv-antibodies were expressed as soluble recombinant proteins, and their binding affinities were assessed using a surface plasmon resonance biosensor. The binding regions of these Fv-antibodies corresponded to the cleavage sites of furin (S1/S2) and transmembrane serine protease 2 (TMPRSS2, S2'). The neutralizing activities of the two Fv-antibodies were demonstrated using a cell-based infection assay with pseudo-viruses carrying the SP of four different SARS-CoV-2 variants: wild-type (D614), delta (B.1.617.2), omicron (BA.2), and omicron (BA.4/5).