Viral infectious diseases are a serious global health threat. For many viruses, safe vaccines and specific antiviral treatments are yet unavailable. Our work has focused on neglected arboviruses like dengue, West Nile, Zika and Chikungunya, annually infecting hundreds of millions of people. We target viral proteases as the Achilles heel of viral replication, aiming to provide broad-spectrum antiviral agents that may also be effective against newly emerging viruses. Because proteases recognise and cleave polypeptide substrates, peptides are appealing starting points to target them. We have explored different strategies how peptides with noncanonical modifications can selectively inhibit and probe viral proteases, ranging from genetically encoded peptide libraries to new synthetic methodologies that allow for direct peptide modification in biochemical assays. The presentation will also cover prospects for targeting the main protease of the novel coronavirus SARS-CoV-2.