Anti-Viral Activity of Ag+ Ions for Viral Prevention, Replication, Cell Surface Receptors, Virus Cleavage, and DNA damage by Ag- DNA Interactions

Silver ions from dissolved silver nitrate; Silver nitrate (AgNO3): AgNO3→Ag+ + NO3- Silver nanoparticles (AgNPs): Ag0 + (oxidant)→ Ag++ (oxidant)-, and Ag+ + Lx- → AgL(x-1), L is ligand. These free Ag+ ions are capable to react with binding virus surface receptor proteins. AgNPs show anti-inflammatory properties in both animal models and in clinic. Immunomodulatory action of nanosilver has been appeared to modulate the immune system in a beneficial way, containing 1% (w/w) nanocrystalline silver suppressed two proinflammatory cytokines, II. 12 and TNFα, known to be involved in allergic skin diseases. AgNPs can be used as potential therapeutics for inhibiting outbreaks of influenza. Nanosilver can prevent HIV from connecting to CD4 that at the first stages of HIV proliferation, silver nanoparticles can act as antivirus agent for deactivation of the virus in a short period of time. Further, silver nanoparticles are important efficient for preventing viral infection against Ebola virus, HIV-1, H1N1 influenza, Herpes simplex, Hepatitis B, Tacaribe, RSV, HSV-2, Entrovirus, Chikungunya virus by blocking of viral attachment and entry steps. Chitin/chitosan with nanoscale fiber-like and porous surface structures may absorb heavy metals. Silver nanoparticles exert anti-HIV activity at an early stage of viral replication, most likely as a virucidal agent or as an inhibitor of viral entry that AgNPs bind to gp1 20 in a manner that prevents CD-dependent virion binding, fusion, and infectivity, acting as an effective virucidal agent against cell-free virus (laboratory strains, clinical isolates, T and M tropic strains, and resistant strains) and cell-associated virus, besides AgNPs inhibit post-entry stages of the HIV-1 life cycle. In addition, tannic acid modified AgNPs have the ability to prevent HSV-2 infection by direct inhibition of virus attachment, penetration and post-infection spread.
Viral neuraminidase can be assumed that the neuraminidase enzyme is corresponded to enzyme of bacterial peptidoglycan (PGN) autolysin. When viral neuraminidase enzyme is activated, and virus protein homeostasis is lost, virus degradation proceeds, in which virus leads to apoptotic death and the virus is destroyed. Ag+ ions induced viral neuraminidase activations are enhanced in action sites of virus, subsequently the virus growth is suppressed,and virus destruction occurs. The influenza virus HA is the viral protein that attaches to cell receptors that the HA plays an important role in the release of the viral RNA into the cell, by causing fusion of viral and cellular membrane. HA must be cleaved by cellular proteases to be active as a fusion protein. The other, endolysin is a PGN-hydrolysing enzyme that carries out enzymic digestion of the cell wall PGN at the end of the phage infection cycle, which ensure the release of newly packed phage particles. Hence, these phage particles like virus particles react with cell surface as viral receptor-binding protein, suggesting that leads to virus apoptotic death.

Substituting of Ag+ ions into hydrogen bonds in DNA base-pairing G≡C and A=T pairs respectively, it may be considered that DNA damages due to silver-complex formation within DNA base-pairs G≡C, A=T occur in cytoplasm of cancer cell. Silver atom is twofold coordinated by two N atoms, and N-Ag+-N complex of linear type is formed in DNA base pairs. In ground state, O-Ag+-N, N-Ag+-N, N-Ag+-O twofold coordinated linear type may be formed at the G≡C pair, and whereas, N-Ag+-O, N-Ag+-N complexes of twofold coordinated linear type may be formed at the A =T pair. A=T base pairs are less stable than G≡C base pairs in Ag+-DNA.

Keywords: PGN autolysin, Silver nitrate and AgNPs, Virucide, Viral prevention and replication, Viral hydrolase and degradation, Neuraminidase, Cell surface receptor, Viral destruction, Virus cleavage.