Characterization of a 66 kDa Secretory Protein of Haemonchus contortus and Its Effect on Host Mononuclear Cells

Sokkalingam, Murugavel; Samal, Amir Kumar; Thangavelu, Lakshmi; Joshi, Pallavi

doi:10.1007/s40011-019-01162-1

Cited by 1 publication

(2 citation statements)

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“…GDH has already been accepted as a potential target for anthelmintics [ 51 ] because of “significant differences” in the amino acid sequence between the host and the parasite enzyme [ 52 ]. It is also capable of inhibiting monocyte functions leading to impaired immune function [ 49 ]. Antibodies against GDH are present in the sera of H. contortus -infected animals, showing that the protein is well recognized by the host immune effectors cells [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

“…contortus secretes a variety of proteins for survival, which are anticoagulant [42], as well as immunomodulatory [43,44,45,46,47]; and also play a role in the regulation of gut pH [48]. Amongst these proteins, a 66 kDa GDH enzyme [49] catalyzes the oxidative deamination of glutamate with the formation of α-ketoglutarate and NH 4 þ . In general, helminth GDH is more active with NADþ/NADH compared with NADPþ/NADPH [50] and is expressed exclusively during the blood-feeding stages of H. contortus.…”

Section: Discussionmentioning

confidence: 99%

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In silico to In vivo development of a polyherbal against Haemonchus contortus

Rahal

Sharma

Kumar

et al. 2022

Heliyon

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Haemonchus contortus is a major constraint in the development of small ruminant subsector due to significant production losses incurred by it. The present study explores the antiparasitic potential of three anthelmintic plants ( Butea monosperma, Vitex negundo and Catharanthus roseus (L.) G.Don ) against H . contortus taking albendazole as the standard. In silico molecular docking and pharmacokinetic prediction studies were conducted with known bioactive molecules of these plants (palasonin, vinblastine, vincristine, betulinic acid and ursolic acid) against Glutamate Dehydrogenase (GDH) and tubulin molecules of the parasite. Methanolic extracts of these herbs were fractionated (hexane, ethyl acetate, chloroform and methanol) and used in in vitro larvicidal studies. Based on the in vitro data, two herbal prototypes were developed and clinically tested. All the 5 ligand molecules showed better binding affnity for GDH and tubulin protein as compared with albendazole and shared similar binding site in the core of the GDH hexamer with slight variations. Albendazole approximately stacked against GLY190A residue, showing hydrophobic interactions with PRO157A and a Pi-cation electrostatic interaction with ARG390 along with four hydrogen bonds. Vincristine formed 2 pi-anionic electrostatic bonds with ASP158 of B and C subunits alongwith hydrogen bonding and hydrophobic interaction and an additional pi-anion electrostatic interaction at ASP158A for vinblastine. Albendazole bound to α-tubulin next to colchicine site whereas vinblastine is bound at the nearby laulimalide/peloruside site of the dimer. Betulinic acid showed lateral interaction between the H2–H3 loop of one alpha subunit and H10 of the adjacent alpha subunit of two tubulin dimers. Ursolic acid and palasonin bound at the intradimer N site of microtubulin involving the H1–H7 and H1–H2 zone, respectively. The in vitro studies demonstrated good dose dependent anthelmintic potential. Both the prototypes were quite efficacious in clearing the infection, keeping it to a minimal for more than 5 months, probably, through direct anthelmintic effect through GDH, tubulin depolymerization and uncoupling as well as indirectly through immunomodulation along with antioxidant and anti-inflammatory properties.

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Section: Discussionmentioning

confidence: 99%