SARS-CoV-2 targets the respiratory system, yet ACE2 mRNA expression is low in the lungs. Viral entry in these low-expressing tissues may be caused by the structure of the virus's S protein. The furin cleaving site at the S1-S2 junction, where the S1 and S2 subunits of the S protein meet, is not present in other SARS viruses. Studies with SARS-CoV show that inserting a cleavage site at this location modestly but significantly increases membrane fusion, possibly aiding infection in low ACE2 expressing tissue.