We propose to develop a novel therapeutic for respiratory viruses, including all current and predicted SARSCoV- 2 variants, other coronaviruses, influenza, and paramyxo/pneumoviruses—using a peptidomimetic small molecule approach targeting TMPRSS2 and other trypsin-like proteases (TTSP) that are essential for virus entry. We expect our therapeutic platform to be applicable and effective for prophylactic use, and so we will target virus transmission studies in vivo. As our system is based on simple-to-synthesize peptides, which act outside of the cell, is it expected to be cost–effective, and our approach is specifically designed to cover a range of distinct viruses. However, it is important to note that our platform is highly flexible, and be applicable in the face of a novel viruses that may emerge, without significance anti-viral resistance (as it is host-targeted).