Significance of the optimized S1 / S2 restriction site for SARS-CoV-2 infection (SARS_S1S2)

As part of the already funded coronavirus project (BMBF-Verbund RAPID: Risk assessment in prepandemic respiratory infectious diseases, subproject 4: Efficiency of the proteolytic activation of respiratory viruses as a marker for pandemic potential), it is investigated whether naturally occurring MERS-CoV variants represent an increased pandemic Show potential. A virus variant was identified in patients in Saudi Arabia that carries the T746K exchange at the S1 / S2 interface of the viral spike protein (S). This exchange leads to the fact that the cleavage of the S protein at the S1 / S2 interface is intensified by the cellular protease furin in infected cells. Also increased the exchange of virus entry into lung cells, which depends on the activation of the S protein by the cellular protease TMPRSS2. Finally, the exchange increases the resistance to the interferon-induced host cell factors GBP2 and GBP5. To what extent T746K increases the virus spread in primary lung epithelium in vitro and the viral spread and pathogenesis in experimentally infected marmosets is unclear and is being investigated in the ongoing project.