Dödligt virus från Kina orsakar panik (SARS-CoV-2, COVID-19)

The furin sequence motif at S1/S2 site is missing in all SARS/SARSr virus Spike protein, raising an interesting question on whether this furin sequence motif in 2019-nCoV is entirely novel

Taken together, the furin motif at S1/S2 site of 2019-nCoV might be not only functional but also the main site for host cell cleavage.This PRRARSV furin cleavage sequence motif is located at the boundary of the two subunits of 2019-nCoV S protein and is exposed (ref 4,5,6,13). It matches to the furin site in Aerolysin (FurinDB search) and was predicated as a furin cleavage site by ProP program. Therefore, it’s reasonable to consider the possibility that 2019-nCoV, unlike SARS virus, utilizes furin cleavage mechanism to gain effective membrane fusion and host cell entry. Furin is ubiquitously expressed and trafficked to the trans-Golgi network or recycled to the cell surface through the endosomal system (Ref 9). Furin plays a crucial role in the activation of the otherwise inactive membrane fusion and host cell entry via S2 domain of the spike protein of type 2 and type 3 coronaviruses (Ref. 7,8, 9,10). The identification of a putative furin site in 2019-nCoV virus spike protein underscores the importance of experimentally determining if furin is indeed involved in the infectivity and pathogenicity of the new 2019-nCoV infection. A recent report has showed that after S1 binding to ACE2 receptor, and most likely the subsequent cleavage of S1 and S2, the heptad repeats HR1 and HR2 in 2019-nCoV are involved in the actual fusion with cell membrane (ref 15)