IN-SILICO IDENTIFICATION OF POTENTIAL DRUG TARGETS FOR BOVINE ONCHOCERCIASIS USING PROTEINS FROM METABOLIC PATHWAYS OF Wolbachia ENDOSYMBIONT OF Onchocercaochengi
IN-SILICO IDENTIFICATION OF POTENTIAL DRUG TARGETS FOR BOVINE ONCHOCERCIASIS USING PROTEINS FROM METABOLIC PATHWAYS OF Wolbachia ENDOSYMBIONT OF Onchocercaochengi
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Date
2021-05
Authors
OKPOKO, Cheluchi Solumtochukwu
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Abstract
Chemotherapy with antibiotics against the Wolbachia endosymbiont is a method of
eliminating adult filarial parasites. Unfortunately, rapidly evolving drug resistance to
antibiotics is limiting the use of these drugs against Gram-negative bacteria, thereby
demanding novel approaches in drug target identification and chemotherapy.
In-silico approaches offer a more rapid and cost effective strategy in drug discovery and
design. In this study, computational techniques which involved a systematic protein
subtractive approach, were employed to identify putative drug targets for bovine
onchocerciasis, as a model of filariasis, using the biological pathways of Wolbachia
endosymbiont of Onchocerca ochengi (wOo) available in KEGG (Kyoto Encyclopedia of
Genes and Genomes). This study identified a total of 70 biological pathways of wOo from
KEGG, with 13 of these pathways being unique to wOo and 57 being common to both cattle
(Bos taurus) and wOo. Out of 349 proteins associated with the 70 pathways of Wolbachia of
Onchocerca ochengi, 204 proteins were identified as non-homologous to cattle proteins by
NCBI BLAST search tool. From the 204 proteins, 180 proteins were further identified as
essential to the survival of Wolbachia of Onchocerca ochengi using DEG (Database of
Essential genes). Prioritization of the resultant 180 proteins revealed 58 proteins as druggable
targets for bovine onchocerciasis. Molecular docking studies of the three dimensional
structures of these 58 proteins with 36 drug structures from drug bank database resulted in
only 32 proteins of wOo completing the molecular docking process. This study therefore
revealed 32 drug targets for bovine onchocerciasis. Molecular docking results of malic
enzyme with NADH, N5-carboxyaminoimidazole ribonucleotide synthase with carglumic
acid and replicative DNA helicase with zinc showed the best, moderate and least binding
energies repectively. This study has identified potential drug targets of wOo for bovine
onchocerciasis, towards control of human onchocerciasis
Description
A THESIS SUBMITTED TO THE SCHOOL OF POSTGRADUATE STUDIES,
AHMADU BELLO UNIVERSITY IN PARTIAL FULFILLMENT FOR THE
AWARD OF MASTER DEGREE IN BIOTECHNOLOGY
DEPARTMENT OF BIOCHEMISTRY,
FACULTY OF LIFE SCIENCES
AHMADU BELLO UNIVERSITY,
ZARIA, NIGERIA
Keywords
IN-SILICO IDENTIFICATION,, POTENTIAL DRUG TARGETS,, BOVINE ONCHOCERCIASIS,, PROTEINS,, METABOLIC PATHWAYS,, Wolbachia ENDOSYMBIONT,, Onchocercaochengi.