Cysteine proteases are hydrolases that may play a key role in different disease states caused by trypanosomatids and cancerous cells. Our primary question relates to how much chemical diversity we have in the chemical space of cysteine proteases and how many chemicals we need to synthesize to navigate the entire space and identify only those classified at their intersection. The chemical space may consist of small chemical substances containing only C, N, O, S, and halogens which may contain more than 10^60 molecules. In addition to the enumeration we still need to understand and navigate the entire chemical universe of molecules for the realization of virtual screening and machine learning. In this presentation, I intend to show how the Medicinal Chemistry Group of the Institute of Chemistry of São Carlos of the University of São Paulo (NEQUIMED/IQSC/USP) is using computational methods to help in the discovery of new trypanocidal agents for the treatment of Chagas disease and leishmaniasis as well as pancreatic cancer. FAPESP/CNPq /CAPES/SDC/SEAGATE.