Glycogen synthase kinase 3B prediction as primary cellular target to mediate anti hepatitis C effect of nitazoxanide

ملخص البحث

Hepatitis C is a major healthcare problem that launched the quest and the interest of scientists to search for solutions that alleviate its risks. New groups of drugs are developed and repurposed for this reason. One of the drugs that recently repurposed to be used as an anti-HCV drug is Nitazoxanide (NTZ). NTZ is mainly athiazolide antiparasitic drug that is mainly used for the treatment of cryptosporidiosis and giardiasis . Tizoxanide (TIZ), which is the active metabolite of NTZ, was recently reported to be active against some viruses including hepatitis C virus (HCV). The anti-HCV mode of action of Nitazoxanide is the overproduction of the hyperphosphorylated HCV non-structural protein 5 A (NS5A). However, the exact mechanism of action is not so clear. Some previous works suggested one member of the CMGC Serine/Threonine protein kinase family to be the primary cellular target of NTZ. A more recent work revealed that NS5A is a direct substrate of casein kinase I a (CKIa). However, no direct effect of NTZ or TIZ was reported on CKIa in enzymatic assays. In this work, starting with the chemical structure of NTZ and TIZ, some in-silico approaches were applied to hypothesize the human primary cellular target for NTZ. Accordingly, glycogen synthase kinase 3b (GSK3b), a ember of CMGC Serine/Threonine protein kinase family, was retrieved as a proposed target of NTZ that is likely mediating its anti-HCV effect.

مكان النشر:

International research journal of pharmacy، العدد 4 (11): 37-39.

تاريخ البحث:

2013

الكلمات الدلالية:

drug repurposing, Nitazoxanide mode of action, Similarity ensemble approach, pharmacophore mapping.

ملفات: