Antiviral Activities of Ferrous and Ferric Iron in Viral Prevention, Entry and Uncoating, Replication, mRNA Degradation and DNA/RNA Virus Replication, and Release and Budding along Viral Life Cycle

Iron is important trace element in the human body that the absorption of iron is strictly controlled through hepcidin, while there are no efficient physiologic mechanisms to excrete iron from the body, in which cellular iron homeostasis is controlled by iron uptake at the plasma membrane. Viruses are the smallest pathogens and consisted of a single nuclei acid (RNA or DNA) encased in a protein shell which are covered with a lipid-containing membrane. A virus infection depends on factors both in the virus and the host that the most important factor in a virus is genomic alterations which the viral life cycle of a virus starts with its entry into a host. Iron regulator hepcidin has a direct antiviral activity against HCV replication. Iron is released from transferrin within the endocytic vesicle and reduced, Fe(Ⅱ) is transported across the endosomal membrane by the permease DMT1. Fe2+ chelator (BIP) inhibits DNA virus replication. Fe(Ⅲ) inhibits replication of DNA and RNA viruses.

Lactoferrin has effective antiviral activity for viral prevention, enveloped and naked viruses such as rotavirus, enterovirus, and adenovirus. TfR1 plays a role in HCV infection at the level of glycoprotein-mediated entry. Iron can be toxic when present in excess for its capacity to donate electrons to oxygen, thus causing the ROS generation of superoxide anions and hydroxyl radicals, superoxide hydrogen, and copious ROS and RNS are synthesized. Oxygen consumption in the peroxisome leads to H2O2 production, and H2O2 releases into the cytosol which contributes to oxidative stress. Chelators of DFO and deferiprone are ideal candidates for use during co-infection and excess iron situations because they have been implicated in HIV replication inhibition. The evolution of iron chelators from a range of primordial siderophores and aromatic heterocyclic ligands has led to the formation of a new generation of potent and efficient iron chelators.

Keywords: Ferrous and ferric ions, Iron deficiency and overload, HIV replication, HCV infection, Lactoferrin, Ferroportein, DMT, DFO, ROS, Iron chelation.