Isolation and characterization of an anti‐leishmanial disintegrin from Cerastes cerastes venom

Abstract

Investigating new antimicrobial and antiparasitic components from Viperidae venoms represents an alternative therapeutic strategy. In this study, we report the characterization of a disintegrin isolated from Cerastes cerastes venom, exhibiting antiparasitic activity on Leishmania infantum promastigotes. Indeed, isolated disintegrin, referred to Disintegrin_Cc, induced 84.75% of parasiticidal activity and deep morphological alterations on the parasites. SDS-PAGE analysis indicated that this disintegrin was homogenous. This dimeric disintegrin of 14,193.97 Da contains an RGD domain and four intramolecular disulfide bridges. It presents a high percentage of identity with other related snake disintegrins. Predicted 3D structure indicated that this peptide shares partial homology with well-known active antimicrobial peptides. Disintegrin_Cc inhibited 80% of arachidonic acid-induced platelet aggregation. The obtained results suggest that the isolated molecule plays a dual role as a disintegrin and as an anti-leishmanial compound. This component could be useful as a drug in the treatment of leishmaniasis.

Screening Snake Venoms for Toxicity to Tetrahymena Pyriformis Revealed Anti-Protozoan Activity of Cobra Cytotoxins

“…In particular, they include phospholipases A2 [6], L-amino acid oxidases [7] and cathelicidins [8]. Venoms of several snake species were shown to be toxic to protozoans [9][10][11][12] and identification of proteins manifesting anti-protozoan activity in viperid venoms revealed that phospholipase A2 [22], metalloproteinase [23], L-amino acid oxidase [24] and disintegrin [14] are toxic to different protozoa. For example, BnSP-7 toxin, a catalytically inactive phospholipase A2 from Bothrops pauloensis snake venom, showed activity against promastigote Leishmania amazonensis parasite forms, inhibiting parasite proliferation by 60-70% at toxin concentrations of 50-200 µg/mL 96 h after treatment [22].…”

“…It was also reported that the venom of the cobra Naja nigricollis possessed the capacity to kill Trypanosoma brucei, a parasitic protozoan [13]. Furthermore, a disintegrin isolated from Cerastes cerastes venom exhibited antiparasitic activity on Leishmania infantum promastigotes [14].…”

The Potassium Channel Blocker β-Bungarotoxin from the Krait Bungarus multicinctus Venom Manifests Antiprotozoal Activity

“…It should also be noted that cysteine-rich secretory protein (CRISP) crovinin from the venom of C. viridis viridis showed an IC50 of 1–2 μg/mL, depending on the type of parasitic protozoan [ 27 ]. In addition, disintegrin from the venom of Cerastes cerastes was toxic to L. infantum promastigotes [ 23 ] at a concentration of 0.1 μg/mL, causing the death of 97.6% of promastigotes after 72 h [ 23 ]. Earlier, we have shown that cobra cytotoxins at a concentration of 1 mg/mL kill all Tetrahymena cells within several minutes [ 14 ].…”

“…[ 8 ], Naja nigricollis [ 19 ] and some other species, as well as metalloproteases from the venoms of B. neuwiedi [ 20 ] and B. moojeni [ 21 ]. Non-enzymatic toxins include a lectin from B. leucurus venom [ 22 ], a disintegrin from Cerastes cerastes venom [ 23 ], a small pore-forming myotoxin crotamine from Crotalus venom [ 24 ], cathelicidin-like proteins crotalicidin and batroxicidin from C. durissus terrificus and B. atrox venoms [ 25 , 26 ], a CRiSP crovirin from C. viridis [ 27 ], and cytotoxins from cobra venoms [ 14 ]. It should be noted that the antiprotozoal activity of snake toxins may partially depend on the species of protozoa studied, although such data have not yet been systematized.…”