Abubaker, M. | bioRxiv Science

bioRxiv2019

Immunoinformatics Prediction of Epitope Based Peptide Vaccine Against Listeria Monocytogenes Fructose Bisphosphate Aldolase Protein

Listeria Monocytogenes represents an important food-borne pathogen worldwide that can cause life-threatening listeriosis disease especially in pregnant women, fetuses, elderly people, and immuno-compromised individuals with high mortality rates. Moreover, no vaccine against it exists. This study predicts an effective epitope-based vaccine against Fructose 1,6 Bisphosphate Aldolase (FBA) enzyme of Listeria Monocytogenes using immunoinformatics approaches. The sequences were retrieved from NCBI and several prediction tests were conducted to analyze possible epitopes for B-cell, T-cell MHC class I and II. 3D structure of the promising epitopes was obtained. Two epitopes showed high binding affinity for B-cells, while four epitopes showed high binding affinity for MHCI and MHCII. The results were promising to formulate a vaccine with more than 98% population coverage. We hope that these promising epitopes serves as a preventive measure for the disease in the future and recommend invivo and invitro studies.

bioinformatics↗

bioRxiv2019

Lead optimisation of dehydroemetine for repositioned use in malaria

Drug repositioning offers an effective alternative to de novo drug design to tackle the urgent need for novel anti-malarial treatments. The anti-amoebic compound, emetine dihydrochloride, has been identified as a potent in-vitro inhibitor of the multi-drug resistant strain K1 of Plasmodium falciparum (IC50: 47 nM + 2.1 nM). 2,3-dehydroemetine, a synthetic analogue of emetine dihydrochloride has been claimed to have less cardiotoxic effects than emetine. The structures of two diastereoisomers of 2,3-dehydroemetine were modelled on the reported emetine binding site on cryo-EM structure 3J7A and it was found that (-)-R,S-dehydroemetine mimicked the bound pose of emetine more closely than (-)-S,S-dehydroisoemetine. (-)-R,S-dehydroemetine was also found to be highly potent against the multi-drug resistant K1 strain of P. falciparum in comparison with (-)-S,S-dehydroisoemetine, which loses its potency due to the change of configuration at C-1. In addition to its effect on the asexual erythrocytic stages of P. falciparum, the compounds exhibited gametocidal properties with no cross-resistance against any of the multi-drug resistant strains tested. Drug interaction studies showed (-)-R,S-dehydroemetine to have synergistic antimalarial activity with atovaquone and proguanil. Emetine dihydrochloride, and (-)-R,S-dehydroemetine failed to show any inhibition of the hERG potassium channel and displayed atovoquone-like activity on the mitochondrial membrane potential.

microbiology↗