sja-6017 and Chagas-Disease

Cysteine proteases comprise an important class of drug targets, especially for infectious diseases such as Chagas disease (cruzain) and COVID-19 (3CL protease, cathepsin L). Peptide aldehydes have proven to be potent inhibitors for all of these proteases. However, the intrinsic, high electrophilicity of the aldehyde group is associated with safety concerns and metabolic instability, limiting the use of aldehyde inhibitors as drugs. We have developed a novel class of self-masked aldehyde inhibitors (SMAIs) for cruzain, the major cysteine protease of the causative agent of Chagas disease-

Topics: Aldehydes; Cathepsin L; Chagas Disease; COVID-19 Drug Treatment; Cysteine Endopeptidases; Cysteine Proteases; Cysteine Proteinase Inhibitors; Drug Design; Humans; Kinetics; Models, Molecular; Molecular Structure; Protozoan Proteins; SARS-CoV-2; Structure-Activity Relationship; Trypanosoma cruzi