Palmitoyl-protein thioesterase 1, viral nucleocapsid, and heme polymerase

This target entry represents a heterogeneous group of molecular targets associated with the mechanism of action of 4-aminoquinoline drugs like chloroquine and hydroxychloroquine. Palmitoyl-protein thioesterase 1 (PPT1) is a lysosomal enzyme (UniProt P50897) that removes thioester-linked fatty acyl groups from cysteine residues; its inhibition leads to lysosomal membrane permeabilization and autophagy inhibition, which is a strategy being investigated in cancer therapy (Rebecca et al., 2019, Cancer Discovery). The viral nucleocapsid protein is a structural protein that packages the viral RNA genome into a helical ribonucleoprotein complex, essential for viral replication and assembly in viruses such as SARS-CoV-2 (PubMed 32425134). Heme polymerase (also known as heme biocrystallization) is a process in Plasmodium parasites where toxic free heme is sequestered into non-toxic hemozoin; inhibition of this process is the primary mechanism of antimalarial drugs (Sullivan et al., 1996, PNAS). Because this entry combines multiple distinct proteins and biochemical processes into a single label, it is classified as an incorrect or overly broad target definition. These targets are collectively involved in infectious diseases, oncology, and lysosomal storage disorders.

Other names

PPT1Palmitoyl-protein thioesterase 1Nucleocapsid proteinN proteinHeme polymeraseHeme biocrystallizationHeme detoxification proteinHDPQuinone reductase 2NQO2

Inhibition of lysosomal thioesterase activity, interference with viral RNA packaging, and inhibition of heme-to-hemozoin conversion.