GLYCOGEN SYNTHASE KINASE 3Î’ PREDICTION AS PRIMARY CELLULAR TARGET TO MEDIATE ANTI HEPATITIS C EFFECT OF NITAZOXANIDE

Abstract

Hepati tis C is a major healthcare problem that launched the quest and the interest of scientists to search for solutions that allev iate its risks. New groups of drugs are developed and repurposed for this reason. One of the drugs that recently repurposed to be u sed as an anti - HCV drug is Nitazoxanide (NTZ). NTZ is mainly a thiazolide antip arasitic 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 act ive against some viruses including hepatitis C virus (HCV) . T he anti - HCV mode of act ion 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. S ome pr evious works suggested one member of the CMGC Ser ine /Th re onine 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 α (CKI α ) . However, no direct effect of NTZ or TIZ was reported on CKI α in enzymatic assays. In this work, starting with the chemical structure of NTZ and TIZ, some in - silico approaches were applie d to hypothesize the human primary cellular target for NTZ. Accordingly, glycogen synthase kinase 3 β (GSK3 β ), a member of CMGC Serine/Threonine protein kinase family, was retrieved as a proposed target of NTZ that is likely mediating its anti - HCV effect.