Anti-viral vaccine activity of Zn2+ ions for viral prevention, pathogenesis processes, and ROS generation causing to oxidative stress have been investigated. AZP is efficient for viral prevention by inhibitions of BSCTV and DNA virus replications. The AZP phenotypes show strongly resistant to virus infection and viral DNA replication could be applied to the prevention of virus infections in humans. ZnOTs exhibit the ability to neutralize HSV-2 virions and blocking HSV-2 attachment activity. Zinc salts can mediate antiviral activity on RSV by altering the ability of the cell to support RSV replication. The effect of zinc sulfate on seroconversion after a simple method vaccination had been identified that accelerated HB vaccination can shorten duration of immunization of this clinical trial for showing its effectiveness. The inhibition of zinc binding activity of hMPV M2-1 protein can lead to the development of novel, live attenuated vaccines as well as antiviral drugs for pneumoviruses. The CCHH zinc finger motif provides potential vaccine candidates for the development of live species-specific attenuated influenza virus vaccines. Chelates zinc ions inhibit HIV-1 replication. The LAIVs are attracting attention as several advantages over inactivated vaccines. Zinc finger reactive compounds also inactivate retroviruses. ZOTEN promoted the presentation of bound HSV-2 virions. The regulated ZFNs in the presence of HIV-1 Tat may provide a safer and novel genome-editing technology for eradicating HIV-1 proviral DNA from infected host cells. Zinc ions inhibit vaccine virus growth. The ZAP inhibits HIV-1 infection by viral mRNAs degradation. ZAP also inhibits the spreading against XMRV. The treatment of viral infections with viral spreading will be achieved and improved the therapeutic effects by using zinc oxide nanoparticles. ROS and RNS within viruses of viral entry, viral replication, and viral spread are generated in all situations. ROS in virus pathogenesis play an important role in cell signaling and regulate hormone action, growth factors, cytokines, transcription, apoptosis, immunomodulation, and neuromodulation, leading to chronic oxidative stress. Oxidative stress has been occurred in various viral infections. The antioxidant components lead to an excess storage of H2O2, which further increases the hydroxyl radicals and lipid peroxide that signal the cell to undergo a programmed cell death. Thus, zinc-associated vaccine activity mechanism against viruses is indicated that the anti-viral vaccine activity of released Zn2+ ions from zinc solutions and ZnO NPs, may be enhanced by Zn2+ ion-induced Zn2+ ions-coordinated adapted immunity, viral growth regulation, and viral apoptosis and death.