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Abstract Over the past century a number of synthetic antiviral agents had been discovered and developed but lack of efficiency, Drug resistance and side effects are still the major hindrances to gain successful therapeutic outcomes (Richman, 2006). Regarding that fact there was an urgent need for continuous research for new antiviral agents especially derived from natural products. The antiviral activity and mode of action of milk proteins, yogurt as a fermented food and milk whey of different sources of milk, in addition to honey, against Enteric viruses as Cox B3 virus, Rotavirus and Adenovirus 40 were investigated in the preceding chapters of this thesis. In Chapter 1 and 2, presented an introduction into the problem and more details about the history, structure, replication, pathogenesis, and epidemiology of Adenovirus, Rotavirus and Coxsackie virus, in addition to the current situation of potential treatment or therapeutic for each virus. Finally vision and objectives for solving the problem in the current thesis have been cleared. This study was design to investigate and to determine the antiviral activity of metabolites extracted from different sources of milk products as whey and yogurt, in addition to lactoferrin protein in vitro and in vivo. This had been performed using cell culture assays, qualitative scoring of cytopathic effect (CPE). The work also aimed to determine the mode of action of such metabolites, whether it acts directly on the virus, the cells or both, in sequence experiments that will look at the protective and neutralizing capabilities of milk metabolites. Finally, the effects of various thermal treatment of milk antiviral activity of yogurt and whey metabolites have also examined. The results of this work could be summarized in the following points; A- Bovine lactoferrin, yogurt metabolites as a fermented food and milk whey metabolites of different sources of milk had significant inhibitory effects on the development of infection caused by enteric viruses with high percentage up to more than 90 %. B- Camel Bio-yogurt metabolite, Lactoferrin Protein, Camel yogurt metabolite and Bovine Bio-yogurt exhibited the highest antiviral activity against Coxsackie virus giving 95.4%, 94.7%, 91.1% and 90% respectively, while moderate antiviral activity was observed for Buffalo yogurt metabolite (89.9%), Bovine yogurt metabolite (89.2%) and Buffalo Bio-yogurt metabolite (88.3%). Mild antiviral activity was observed for Bovine whey metabolite (78.7 %), Camel whey metabolite (74.5 %) and buffalo whey metabolite (73 %). Honey showed the lowest antiviral activity (32.5 %). In general, all of Yogurt, whey, LF and Bio-yogurt metabolites had high ability of antiviral activity except honey. C- Significant inhibitory effects were detected against Rotavirus in comparison with the control. Bovine yogurt metabolite, Camel Bio-yogurt metabolite, and Lactoferrin Protein were exhibited the strong percentage of antiviral activity against Rotavirus gives 91.5%, 90.3%, and 90.0% respectively, while the moderate antiviral activity was observed for Camel yogurt (88.9%), Buffalo yogurt metabolite (88.0%), Buffalo Bio-yogurt metabolite (86.1%), and Bovine Bioyogurt metabolite (82%). Camel whey metabolite (79%), Bovine whey metabolite (77%) and buffalo whey metabolite (63%) showed mild antiviral activity. And the lowest of antiviral activity was observed for Honey (21.0%). In general, all of Yogurt, whey, LF and Bioyogurt metabolites have high antiviral activity except honey. D- Results also confirmed the significant inhibitory effects against Adenovirus in comparison with a control. All tested metabolites exhibited different percentages of antiviral activity (93%) except honey. Bovine yogurt metabolite, Bovine Bio-yogurt metabolite, and Lactoferrin Protein exhibited the strong percentage of antiviral activity against Adenovirus giving 93%, 92%, and 89.5% respectively, while moderate antiviral activity was observed for Camel bio-yogurt metabolite (85.0%), camel yogurt metabolite (81%). Also, mild antiviral activity was observed for Camel whey metabolite (79%), Bovine whey metabolite (77%) and buffalo bio-yogurt metabolite (66%). The weak antiviral activity was observed for Buffalo whey metabolite and buffalo yogurt metabolite while honey had no any antiviral activity against Adenovirus. Overall, this study support the hypothesis that the fermented food as yogurt, milk proteins as lactoferrin and milk products’ metabolites as whey could be potentially used as an antiviral therapeutic agents to slow down or treat the progression of infection during biological synthesis processes or to protect the cell during viral attachment and prevent the viral infection during viral adsorption. This work suggests that the metabolites extracted from yogurt and whey lost their antiviral activity when milk was pretreated with various heat temperatures at different time intervals. It was established that camel yogurt and whey metabolites were more heat resistant than cow and buffalo yogurt and whey metabolites. This means that the Antiviral activity factors of yogurt and whey metabolites in heat treated camel milk are higher than that of cow and buffalo milk. |