Abstract: The present disclosure provides activatable masked antigen binding proteins comprising an antigen binding protein attached to universal masking moieties by peptide linkers. The universal masking moieties dimerize with each other to form a dimerized masking complex that blocks binding between the antigen binding domain and its target antigen. The individual masking moieties and the dimerized masking complex do not bind specifically to the antigen binding domain. The masking moieties form stable dimers because their association with each other mimics homodimers or heterodimers found in naturally-occurring immunoglobulin or cell receptor molecules. The dimerization of the masking moieties does not involve covalent bonding and can be optimized by engineering interchain association through structure complementarity such as knob-in-hole.

Abstract: The present disclosure provides methods for treating a subject having a coronavirus infection by administering a composition that includes a sACE2 polypeptide to the lungs of a subject infected with a coronavirus. The sACE2 polypeptide includes the extracellular portion of the human ACE2 polypeptide and acts as a decoy, binding the spike (S) protein of coronavirus and thereby preventing the interaction of the S protein with membrane-associated ACE2 expressed on pulmonary cells, thus disrupting the infection process. The sACE2 polypeptide is derived from human ACE2, preventing potential immune reactions of the subject to the therapeutic polypeptide. The sACE2 polypeptide is administered locally to the site of the pathology, avoiding potential adverse effects of systemic delivery.