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. 2021 Mar 11;11:633194. doi: 10.3389/fcimb.2021.633194

Figure 1.

Figure 1

Zinc ditiocarb (ZnDTC), a main metabolite of disulfiram, is potently active against E. histolytica parasites in a preclinical animal model. (A) Disulfiram and its metabolites. (B) ZnDTC is formed from the combination of disulfiram and zinc supplement. (C) Multiple sequence alignment of the conserved metalloprotease motif of COP9 signalosome subunit 5 (CSN5) from E. histolytica and other pathogenic parasites (EHI_050500, TGARI_308590, TcCLB.507083.60, LBRM2903_160015100, ACA1_074760, NF0060740). Identical (green), conserved (blue), semi-conserved (pink) and non-conserved residues (red). (D) Schematic of how ZnDTC inhibits cullin deneddylation by the COP9 signalosome. (E) Representative H&E staining and immunohistochemical analysis of the cecum of infected mice after 5 days of treatment. Specific anti–E. histolytica antibody was used for immunohistochemical staining of trophozoites (brown). Numerous parasites in the infected control, absent in the ZnDTC treated mice and uninfected control. The treatment group received 50 mg/kg disulfiram plus 1 mg/kg zinc gluconate. Panels are reproduced from (Ghosh et al., 2020) with permission.