The current Covid-19 pandemic dramatically illustrates the need to find new anti-viral agents, and underscores the importance of finding these agents before they are needed. Influenza remains a pandemic threat, and resistance is building to many of the current anti-influenza treatments on the market. While antibodies have been found that are broadly effective against multiple strains of influenza, these are not practical to deploy at a population level. As an alternative approach that we believe captures many of the advantages of antibodies in a synthetically tractable molecule, we have used mRNA display under a reprogrammed genetic code (RaPID system) to find a diverse pool of haemagglutinin(HA)-binding macrocyclic peptides. All of these proved to be effective at preventing infection in a cellular assay across several H1 subtypes, and in some cases also H5. Hydrogen-Deuterium exchange footprinting revealed a surprising preference for these to bind to the more conserved 'stem' region of the protein, where the 'head' region is typically dominant for antibody binding. Passaging in the presence of one of these peptide inhibitors led to a resistant virus, but using the HA protein from this virus as bait protein in a follow-up selection campaign revealed new hits that can overcome this resistance. By generating resistance and then overcoming it in the lab before exploiting a hit, a pool of peptides can be developed together as a lead that should be less susceptible to escape when deployed.