Analysing the essential proteins set of Plasmodium falciparum PF3D7 for novel drug targets identification against malaria

Analysing the essential proteins set of Plasmodium falciparum PF3D7 for novel drug targets identification against malaria

Abstract Background Plasmodium falciparum is an obligate intracellular parasite of humans that causes malaria. Falciparum malaria is a major public health threat to human life responsible for high mortality. Currently, the risk of multi-drug resistance of P. falciparum is rapidly increasing. There i...

Full description

Saved in:
Bibliographic Details
Published in:Malaria journal Vol. 20; no. 1; pp. 1 - 11
Main Authors: Ali, Fawad, Wali, Hira, Jan, Saadia, Zia, Asad, Aslam, Muneeba, Ahmad, Imtiaz, Afridi, Sahib Gul, Shams, Sulaiman, Khan, Asifullah
Format: Journal Article
Language:English
Published: London BioMed Central Ltd 03-08-2021
BioMed Central
BMC
Subjects:
Anti-malarial therapeutics
Binding sites
Care and treatment
Comparative proteomics
Diagnosis
Drug resistance
Drug targeting
Drugs
Enzymes
Erythrocytes
Health risks
Human diseases
Hydrogen
Intestinal flora
Intestinal microflora
Lead compounds
Ligands
Localization
Malaria
Methods
Microbiomes
Multidrug resistance
Parasites
Pathogens
Pharmacophore modelling
Plasmodium falciparum
Protein interaction
Proteins
Proteomes
Proteomics
Public health
Risk factors
Testing
Therapeutic targets
Vector-borne diseases
Virulence
Pakistan
Thailand
Asia
Africa
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Background Plasmodium falciparum is an obligate intracellular parasite of humans that causes malaria. Falciparum malaria is a major public health threat to human life responsible for high mortality. Currently, the risk of multi-drug resistance of P. falciparum is rapidly increasing. There is a need to address new anti-malarial therapeutics strategies to combat the drug-resistance threat. Methods The P. falciparum essential proteins were retrieved from the recently published studies . These proteins were initially scanned against human host and its gut microbiome proteome sets by comparative proteomics analyses. The human host non-homologs essential proteins of P. falciparum were additionally analysed for druggability potential via in silico methods to possibly identify novel therapeutic targets. Finally, the PfAp4AH target was prioritized for pharmacophore modelling based virtual screening and molecular docking analyses to identify potent inhibitors from drug-like compounds databases. Results The analyses identified six P. falciparum essential and human host non-homolog proteins that follow the key druggability features. These druggable targets have not been catalogued so far in the Drugbank repository. These prioritized proteins seem novel and promising drug targets against P. falciparum due to their key protein–protein interactions features in pathogen-specific biological pathways and to hold appropriate drug-like molecule binding pockets. The pharmacophore features based virtual screening of Pharmit resource predicted a lead compound i.e. MolPort-045–917-542 as a promising inhibitor of PfAp4AH among prioritized targets. Conclusion The prioritized protein targets may worthy to test in malarial drug discovery programme to overcome the anti-malarial resistance issues. The in-vitro and in-vivo studies might be promising for additional validation of these prioritized lists of drug targets against malaria.
ISSN:1475-2875
1475-2875
DOI:10.1186/s12936-021-03865-1