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Potent Inhibitory Effects of p7 Inhibitors on Genotype 4 HCV-infected Peripheral Blood Mononuclear Cells

Author(s): Maged A. Saleh, Radwa Y. Mekky, Nada El-Ekiaby, Nabila Hamdi, Rasha Ahmed, Abdel Rahman Zekri, Gamal Esmat, Ahmed I. Abdelaziz.

Abstract:

Several patents were published for HCV p7 protein including a synthetic p7 model for drug design and screening of experimental compounds. Additionally, patents were published for identification and use of compounds as p7 inhibitors. HCV p7 protein is a viral ion channel (viroporin) that was found to be crucial for viral production through facilitating assembly and release. Accordingly, targeting the protein is expected to inhibit these stages in the HCV lifecycle. p7 inhibitors displayed effectiveness against recombinant replicons of different HCV genotypes with genotype-dependant responses, but they were never tested on genotype 4 (GT-4). Our study focused on examining the effects of four p7 inhibitors; amantadine, rimantadine, N-nonyl-deoxynojirimycin (NN-DNJ) and hexamethylene amiloride (HMA) on HCV GT-4 for the first time which involves the majority of cases in Egypt and the Middle East-North Africa (MENA) region. HCV viral load was assessed after stimulation by p7 inhibitors for HCV-positive Peripheral Blood Mononuclear Cells (PBMCs) which are known to be extra-hepatic reservoirs for the virus. The compounds showed strong reduction of viral load without affecting cell viability in congruency with previous experimental work that alternatively used other HCV genotypes and cell lines.

Keywords: Amantadine, hexamethylene amiloride (HMA), N-nonyl-deoxynojirimycin (NN-DNJ), p7, PBMCs, rimantadine, Hepatitis C virus (HCV), Genotype 4, p7 inhibitors, extra-hepatic reservoirs, chronic liver disease.

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Article Details

VOLUME: 2
ISSUE: 3
Year: 2012
Page: [227 - 233]
Pages: 7
DOI: 10.2174/2210309011202030227
Price: $100