Described herein fusion proteins comprising modified DPP4 binding sequence and the Fc of a human immunoglobulin, related compositions, and related methods for inhibiting MERS- CoV infection. In addition to the improved potency, the modified DPP4-Fc is also expected to have superior pharmacokinetics, as Fc will confer a long circulating half-life and the ability to be delivered to airway mucosal surfaces, the site of MERS-CoV infection. Unlike antibodies against MERS-CoV, a DPP4-Fc and the modified DPPR-Fc decoy of the invention will not subject the virus to selection for neutralization escape mutants, as any mutation that decreases binding to the decoy will decrease binding to the native receptor, resulting in an attenuated virus.
