**4. Control strategies**

#### **4.1. RNA interference treatment of viral diseases that target mitochondria**

Despite the many advances in molecular biology and in treatment of viral diseases, the prevention and control of viral infections remains a challenge. Alteration of the interaction of the virus and host is one general strategy. Therefore, a complete understanding of the interactions of the host and virus at the molecular level is needed to develop new antiviral drugs and vaccines. There is an urgent need to find more effective therapeutic agents for the treatment of viral infections. Researchers have recently started testing treatments based on RNA interference (RNAi), using either microRNA (miRNA) or small interfering RNA (siRNA). Although this approach is still in its infancy, there has been some success in silencing the viral genes responsible for virulence [73, 74].

RNAi is an endogenous defense that cells use as a defense against harmful nucleic acids, either generated by the cell itself or from external environment (such as a viral invasions) [75]. RNAi is successful against many virus infections, but the delivery and stability of RNAi molecules within the cell are major concerns. The stability of RNAi is affected by its charge and biochemical activity within a cell, so these two parameters must be considered when designing RNAi-based therapies. In addition, the effectiveness of RNAi-based therapies depends on the delivery route [76], target gene [77, 78], target pathogen [75, 78], and target tissue [75]. The adverse effects of using RNAi-based treatment on the environment and treatment costs must also be considered, and we must have a deeper understanding of RNAi at the molecular level. The growing interest of molecular virologists in the use of RNAi suggests that this is one of the most exciting new therapeutic approaches for treatment of viral diseases [75].

#### **4.2. Host antioxidant defense system fights viral invasion**

The increased generation of ROS and reactive nitrogen species (RNS) is a key part of the pathogenesis of many virus infections. OS induces loss of the MMP, so mitochondria are become more susceptible to ROS damage. However, cells also have defenses against ROS, such as reduced glutathione (GSH),which acts as an antioxidant during the oxidative production of ATP in healthy cells [9, 79–81]. An imbalance between the generation of ROS and ROS quenching by the cell's endogenous antioxidant defense system usually leads to a disease and is common during viral invasion. In recent years, due to the unavailability of antiviral drugs, researchers have proposed a number of new strategies to protect against free radical-induced OS. These strategies may be characterized as repair and protection. Protection is achieved by enzymes and by nonenzymatic compounds, such as carotenoids, vitamin C, vitamin E, GSH, and flavonoids [82]. Recent studies have shown the importance of both classes of these molecules in defense against oxidative stress [9, 83–86].
