Version 1
: Received: 8 October 2024 / Approved: 8 October 2024 / Online: 8 October 2024 (10:30:25 CEST)
How to cite:
Abraham, J.; Chauhan, N.; Ray, S. Identifying Drugs That Target Glucokinase for Treating Primary Amoebic Encephalitis (PAM) &Amp; Diabetes. Preprints2024, 2024100551. https://doi.org/10.20944/preprints202410.0551.v1
Abraham, J.; Chauhan, N.; Ray, S. Identifying Drugs That Target Glucokinase for Treating Primary Amoebic Encephalitis (PAM) &Amp; Diabetes. Preprints 2024, 2024100551. https://doi.org/10.20944/preprints202410.0551.v1
Abraham, J.; Chauhan, N.; Ray, S. Identifying Drugs That Target Glucokinase for Treating Primary Amoebic Encephalitis (PAM) &Amp; Diabetes. Preprints2024, 2024100551. https://doi.org/10.20944/preprints202410.0551.v1
APA Style
Abraham, J., Chauhan, N., & Ray, S. (2024). Identifying Drugs That Target Glucokinase for Treating Primary Amoebic Encephalitis (PAM) &Amp; Diabetes. Preprints. https://doi.org/10.20944/preprints202410.0551.v1
Chicago/Turabian Style
Abraham, J., Neha Chauhan and Supriyo Ray. 2024 "Identifying Drugs That Target Glucokinase for Treating Primary Amoebic Encephalitis (PAM) &Amp; Diabetes" Preprints. https://doi.org/10.20944/preprints202410.0551.v1
Abstract
Naegleria fowler, also known as brain-eating amoeba is a thermophilic microorganism that causes primary amoebic encephalitis (PAM) having >98% mortality rate. To date, there are no specific drugs identified to treat this disease. N. fowleri expresses only one form of hexokinase i.e. glucokinase (nGLK) unlike humans that express four isozymes of hexokinase including glucokinase (hexokinase IV) or hGLK that is critical for the first step of glycolysis. Until now, there have not been many studies on glucokinase as a drug target to treat PAM, hence, this study provides an exhaustive analysis of this relatively novel drug target. Thus, it was hypothesized that amoebic glucokinase can arrest carbohydrate metabolism and assist regulating its virulence. To find suitable antagonists to inhibit the activity of nGLK, we first tested the present recommended drugs by the CDC on their ability to bind nGLK. Interestingly our studies show that many of the present recommended drugs can inhibit both amoebic (nGLK) and human (hGLK) homologs of glucokinase. We identified new inhibitors for nGLK and further explored suitable hGLK antagonists for the potential treatment of diabetes. Despite significant structural differences between nGLK and hGLK, it was interesting to note that all our screened inhibitors bound with both nGLK and hGLK. Levomefolic acid; Ziprasidone; and Risperidone were found to be more suited to treat PAM while, Simeprevir; Indacaterol; Crizotinib and Mocetinostat were found to be suited for treating diabetes. The selections were based on multiple criteria including binding affinity; ADME scores; absorption; and its ability to cross the blood brain barrier. This study identifies multiple drugs that have potential not only to treat PAM but also to treat diabetes and also use for lab based biochemical assays for glycolysis inhibitors.
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
