ACE and infection: This manuscript describes a new generation of chimeric ACE-2/Fusion protein hybrid molecules designed to have four important characteristics: (a) ultra-high affinity binding to viral targets; (b) preservation of high affinity binding across variant subgroups; (c) the option of strong silencing of Fc receptor function to minimize ADE of infection or complement antibody-dependent enhancement (C’ADE) and (d) the option of binding to the FcRn receptor to increase biological half-life, particularly in upper respiratory passages.