Figure 7
Proposed model for TMPRSS2–AAT–heparin ternary complexation at the cell surface, preventing activation of the S2 domain. Heparin (red) neutralizes the repulsive electrostatic forces at the TMPRSS2 (wheat)–AAT (blue) interaction rim, in accordance with the predicted binding mode shown in Figs. 6D,E and S5. AAT inhibition of elastase cleavage at the site created by the D614G mutation of the spike protein (B.1.1.7 variant of SARS-CoV-2) is also shown. The inset shows the possibility that one heparin molecule could bridge multiple TMPRSS2–AAT complexes.
