Industrial Pharmacy & 5^th Global Pharmacovigilance Summit

Biography

Biography: Mahmoud F. Elsebai

Abstract

As many as 200 million people worldwide are infected with hepatitis C virus (HCV). About 3–4 million people are infected per year, and more than 350,000 people die yearly from hepatitis C-related diseases (Menzel et al. 2012), (WHO, June 2011). The Egyptian community is suffering from the prevalence of HCV infections (El-Fakharany et al. 2013). Even in the advanced countries hepatitis C is common and there is no any exclusive cure for hepatitis C either naturally or synthetically. HCV is the most common chronic blood-borne infection and it is the most frequent indication for liver transplantation (Haid et al. 2012). In the United States, hepatitis C is the most common chronic blood-borne infection (http://www.cdc.gov/hepatitis/HCV/ index.htm). The infection with HCV is often asymptomatic but chronic infection leads to liver cirrhosis which usually develops into liver failure, liver cancer or life-threatening esophageal and gastric varices. The diseased-liver person usually undergoes subsequent psychological disorders due to the stress of disease which complicates the illness (Takebe et al. 2013). There is no preventive vaccine available for HCV due to its highly mutable nature evidenced by the presence of more than 50 subtypes of HCV; in addition HCV infects only humans and chimpanzees (Houghton 2009). Fortunately, Dorner et al (Dorner et al. 2013) recently, were able to complete the entire HCV life cycle in genetically humanized transgenic mice with stably expressing human CD81 and OCLN and blunting the antiviral immunity in this mice infected with HCV. The standard therapy pegylated interferon plus ribavirin is only effective in 50–60% of patients and is associated with serious side-effects, and half of those which respond relapse after cessation of interferon treatment. HCV treatment(s) have changed dramatically in the era of Direct-Acting Antivirals (DAAs). Currently approved DAAs include NS3/4A protease inhibitors (telaprevir, boceprevir and simeprevir), NS5A inhibitors (daclatasvir and ledipasvir) and the NS5B polymerase inhibitor sofosbuvir. Although these drugs are showing significantly improved efficacy, treatment with these compounds showed rapid emergence of drug resistant mutants are likely to occur and spread between individuals, highly expensive, and narrow spectral activity towards different genotypes of HCV (Berger et al. 2014; Miura et al. 2014; Farnik & Zeuzem 2012). Therefore, therapeutic alternatives are of major importance and hence there is a continued interest in developing further antiviral drugs with altered mechanisms of action and low production costs. In the present study, through joint work with Spanish and Finnish teams, the water extract of the leaves of the wild Egyptian artichoke (WEA) (Cynara cardunculus L. var. sylvestris (Lam.) Fiori) showed improvement of HCV infection symptoms. Therefore, our study was divided into two main strategies: 1) The clinical investigation of WEA extract on some HCV-infected Egyptian patients (approved by the Ethical Committee of Research at the Faculty of Pharmacy, Mansoura University, Egypt, code number 2014/71). The results showed outstanding activity against HCV and its complications such as ascites and jaundice by measuring the PCR, and liver functions such as ALT, AST. 2) The phytochemistry of the WEA extract and its subsequent evaluation of inhibition capacity in vitro using cell-culture derived HCV: The chemical investigation of the WEA extract resulted in the identification of six compounds: a new sesquiterpene lactone (1), in addition to the known compounds (2-6). Their structural elucidation was done by extensive spectroscopic tools such as NMR and HR-MS spectroscopy. The absolute configuration was determined by TDDFT ECD calculations and comparison with the experimental CD spectra. Compounds 1 and 2 were the most potent among the six by using a luciferase-carrying reporter virus (Koutsoudakis et al. 2006). Time-of-addition experiments revealed that compounds 1 and 2 inhibit HCV virus at a time-point during entry. Furthermore, compounds 1 and 2, apart from cell-free infection inhibited HCV cell-cell transmission. Finally, the results showed that