From Chagas to COVID-19 disease: a journey of life?

Cysteine proteases (CPs) are ubiquitous. The vital processes and diseases regulated by CPs make them multifaceted targets in drug discovery and development. However, the delicate balance of their physiological and pathological functions must be adequately shaped by inhibitors. Their applications as diagnostic and prognostic markers are also significant. In this way, our group has been dedicated to the study and design of inhibitors of cruzain from Trypanosoma cruzi, CPA, CPB and CPC from Leishmania spp., SARS-CoV-2 Mpro, as well as human cathepsins L, B and S. Previous proof-of-concept (PoC) studies performed in vitro and in vivo have supported the use of cruzain inhibitors as anti-T. cruzi agents. More recently, with the SARS-CoV-2 pandemic, we repositioned several CP inhibitors, optimized their structures, and identified SARS-CoV-2 Mpro inhibitors with 100 % antiviral efficacy, without observable cytotoxicity.