Antimalarial enzyme conjugates, kits containing same, and methods of producing and using same

A method of killing a Plasmodium-infected erythrocyte in a subject in need of such therapy, comprising:

• administering to the subject an effective amount of an enzyme conjugate comprising a variant cystathione-gamma-lyase (CGL) enzyme conjugated to an annexin ligand, wherein the variant CGL enzyme has L-methioninase activity and has an amino acid sequence that is at least about 95% identical to the amino acid sequence of SEQ ID NO:2 and has substitutions in positions 59, 119, and 339 thereof, or is at least about 95% identical to the amino acid sequence of SEQ ID NO:1 and has substitutions in positions 58, 118, and 338 thereof, and wherein the annexin ligand has the ability to specifically and stably bind to phosphatidylserine (PS) present on an outer surface of the Plasmodium-infected erythrocyte such that the enzyme conjugate is maintained on the outer surface of the infected erythrocyte with substantially no internalization of the enzyme conjugate by the infected erythrocyte, wherein the PS is not present on an outer surface of an uninfected healthy erythrocyte, and wherein the enzyme conjugate is administered absent concurrent therapy with a prodrug acted on by the enzyme conjugate.