3.1.1  Polybasic cleavage site
As evidenced by sequence analysis, there is a residue insertion formed of four amino acids (12 nucleotides) at the boundary between S1 and S2 subunits of the SARS-CoV 2 S. It defines a polybasic furin cleavage site of RRAR for the human SARS-CoV 2 that was absent in human SARS-CoV, bat SARS-like CoVs, and pangolin SARS-like CoV while might be present in other species [3]. After the introduction of mutation to the residue insertion and furin cleavage site, the S1/S2 cleavage of the SARS-CoV 2 S did not longer take place. However, the SARS-CoV 2 S entry raised for VeroE6 cells and remained high in BHK cells that express human ACE. Therefore, it seems that SARS-CoV2 transmissibility does not depend on the S1/S2 cleavage.
A polybasic cleavage site explains a virus that is highly-pathogenic for humans while it is low-pathogenic for other species. For example, using reverse genetic tools, an avian paramyxovirus type 7 (APMV-7) was developed by mutating the fusion (F) protein cleavage site [4]. The constructed APMV-7 showed furin cleavage and increased replication and syncytium formation in cell cultures. However, chicken exposed to the virus did not exhibit infection.