Zinc has been shown to mediate antiviral effects against certain viruses. However, the underlying mechanisms are still largely unknown. We investigated the effects of the two zinc salts, zinc chloride (ZnCl 2 ) and zinc sulfate (ZnSO 4 ), on infection of swine testicle (ST) cells with transmissible gastroenteritis virus (TGEV) and compared it to the effects of a control salt, magnesium sulfate (MgSO 4 ). Virus yield reduction experiments showed that ZnCl 2 and ZnSO 4 did not exhibit direct virucidal effects and did not affect adsorption of TGEV to ST cells. However, ZnCl 2 and ZnSO 4 markedly reduced viral titers as well as TGEV RNA and viral protein synthesis when applied during virus penetration and at different time points after viral cell entry. The results of the study suggest that zinc salts do not interfere with TGEV-cell binding but that they mediate antiviral effects through inhibition of viral penetration or egress or the intracellular phase of the viral life-cycle.