Identification of novel therapeutic candidates inCryptosporidium parvum: anin silicoapproach

Abstract

Unavailability of vaccines and effective drugs are primarily responsible for the growing menace of cryptosporidiosis. This study has incorporated a bioinformatics-based screening approach to explore potential vaccine candidates and novel drug targets in Cryptosporidium parvum proteome. A systematic strategy was defined for comparative genomics, orthology with related Cryptosporidium species, prioritization parameters and MHC class I and II binding promiscuity. The approach reported cytoplasmic protein cgd7_1830, a signal peptide protein, as a novel drug target. SWISS-MODEL online server was used to generate the 3D model of the protein and was validated by PROCHECK. The model has been subjected to in silico docking study with screened potent lead compounds from the ZINC database, PubChem and ChEMBL database using Flare software package of Cresset®. Furthermore, the approach reported protein cgd3_1400, as a vaccine candidate. The predicted B- and T-cell epitopes on the proposed vaccine candidate with highest scores were also subjected to docking study with MHC class I and II alleles using ClusPro web server. Results from this study could facilitate selection of proteins which could serve as drug targets and vaccine candidates to efficiently tackle the growing threat of cryptosporidiosis.

Novel lactate dehydrogenase inhibitors with in vivo efficacy against Cryptosporidium parvum

“…Among the identified potential drug molecular targets, is the C . parvum lactate dehydrogenase (CpLDH), which is a bacterial-type lactate dehydrogenase enzyme that the parasite uses to generate metabolic energy (ATP) in the glycolytic pathway [11, 17, 18]. Importantly, C .…”

“…In C . parvum sporozoites and merozoites, CpLDH is expressed and localized in the cytosol [18], suggesting that it is utilized for energy generation during these parasite stages that are important for host cell invasion and intracellular parasite growth. Interestingly, NSC158011 has been previously shown to inhibit the catalytic activity of the Plasmodium faclciparum phosphoethanolamine methyltransferase enzyme, and to inhibit in vitro intracellular growth of the parasite [23].…”

An update on Cryptosporidium biology and therapeutic avenues

“…The streamlined metabolic pathways of the parasite allow greater opportunities for selective drug therapy (Striepen and Kissinger 2004 ). Various in silico approaches have been employed using comparative genomics analysis, homology modeling, prioritization parameters, epitope prediction, virtual screening, molecular docking, and simulation studies (Dhal et al 2019 ; Panda and Mahapatra 2018 ). In the life cycle of apicomplexan parasites, the regulation of Ca 2+ binding by calcium-dependent protein kinases (CDPKs) is necessary for parasite secretion, motility, and growth (Etzold et al 2014 ).…”