Prevention of poxvirus infection by tetrapyrroles

Abstract

Background: Prevention of poxvirus infection is a topic of great current interest. We report inhibition of vaccinia virus in cell culture by porphyrins and phthalocyanines. Most previous work on the inhibition of viruses with tetrapyrroles has involved photodynamic mechanisms. The current study, however, investigates light-independent inhibition activity.

Methods: The Western Reserve (WR) and International Health Department-J (IHD-J) strains of vaccinia virus were used. Virucidal and antiviral activities as well as the cytotoxicity of test compounds were determined.

Results: Examples of active compounds include zinc protoporphyrin, copper hematoporphyrin, meso(2,6-dihydroxyphenyl)porphyrin, the sulfonated tetra-1-naphthyl and tetra-1-anthracenylporphyrins, selected sulfonated derivatives of halogenated tetraphenyl porphyrins and the copper chelate of tetrasulfonated phthalocyanine. EC50 values for the most active compounds are as low as 0.05 microg/mL (40 nM). One of the most active compounds was the neutral meso(2,6-dihydroxyphenyl)porphyrin, indicating that the compounds do not have to be negatively charged to be active.

Conclusions: Porphyrins and phthalocyanines have been found to be potent inhibitors of infection by vaccinia virus in cell culture. These tetrapyrroles were found to be active against two different virus strains, and against both enveloped and non-enveloped forms of the virus, indicating that these compounds may be broadly effective in their ability to inhibit poxvirus infection.

Figure 1

Structures of tetrapyrroles used in this study.

Figure 2

Prevention of virus infection. TPP[2,6-(OH)2], 50 µg/mL, was incubated with vaccinia virus for 1 h, and then applied to cells. Following virus adsorption, the residual virus-drug mixture was removed and new growth medium added. Plaques were visualized after 2 days (as described in Materials and Methods). (a) WR and (b) IHD-J incubated with CV-1 cells in the absence and presence of TPP [2,6-(OH)2].

Figure 3

Inactivation of vaccinia virus (IHD-J) by selected tetrapyrroles as a function of concentration. Data reported are the averages of triplicate runs; standard deviations are shown.