In silico prediction of new antimicrobial peptides and proteins as druggable targets towards alternative anti-schistosomal therapy

Abidemi Paul Kappo,Marius Belmondo Tincho,Raphael Taiwo Aruleba,Ashley Pretorius

doi:10.1016/j.sciaf.2021.e00804

Abstract

Schistosomiasis is a debilitating disease caused by a parasitic flatworm found in freshwater. With the exponential increase in prevalence, Praziquantel (PZQ) remains the only effective treatment drug, however, resistance to PZQ has been reported recently. Therefore, it is imperative to develop effective alternative anti-schistosomal compounds using bioinformatics-based tools utilizing the broad-spectrum therapeutic capabilities of antimicrobial peptides (AMPs). AMPs are essential components of the innate immune system and are responsible for complete destruction and immunomodulatory effects in the host defence against pathogens. Here, Hidden Markov model was used to identify six anti-microbial peptides (TAK1–TAK6) with potential anti-schistosomal capabilities. Also, glycosyltransferase and axonemal dynein intermediate chain protein were identified as important druggable Schistosome proteins. The 3-D structures of the AMPs and proteins were modelled using I-TASSER and it was shown that the six putative anti-schistosomal AMPs and the two proteins had low C-score, possibly due to lack of available templates for their modelling. Finally, PatchDock was employed to ascertain the interaction between the schistosome proteins and the putative AMPs. All the predicted putative AMPs have good binding affinity to the schistosomal proteins. Overall, the generated AMPs could serve as potential hits in schistosomiasis and could prove effective against drug-resistant schistosomes.

Highlights

Despite the mass drug administration for schistosomiasis it continues to be a major health threat to humans
For the purpose of stochastic model construction, various anti-microbial peptides (AMPs) databases such as Antimicrobial Peptide Database (APD) [13], Collection of Anti-microbial Peptide (CAMP) [14], and PepBank [15] were queried to extract and collect experimentally validated AMPs with anti-parasitic activity
Validated anti-parasitic AMPs were retrieved from various databases as well as the accompanying publication for each AMP

Summary

Introduction

Despite the mass drug administration for schistosomiasis it continues to be a major health threat to humans. The free-living cercaria transforms into schistosomula that travel through the bloodstream to the liver where they develop and mature into adult worms that lay eggs into the bloodstream of the host with these eggs lodging within the host tissue. At this stage, the host suffers difficulty in blood flow, defects in reproductive organs, lungs, brain, and guts, predisposing the patients to genital schistosomiasis, neuro schistosomiasis, hepato-intestinal schistosomiasis and pulmonary schistosomiasis [4]. Some compounds have been proposed to be targets in treating schistosomiasis; these are anti-microbial peptides (AMPs), miltefosine and Imatinib [4,7]

Methods

Results

Discussion

Conclusion