Prevention of poxvirus infection by tetrapyrroles

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.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 μg/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.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.Smallpox, while not found in the world's population at present, remains a potential health hazard especially due to the possibility of its use as a bioweapon [1-5]. There is currently no accepted treatment for smallpox, although a number of agents have been evaluated [6]. Therefore, new therapeutic or virucidal agents could have great utility in slowing both the progression and spread of the disease in an epidemic situation. In the present study, we have investigated the potential of porphyrins (Por) and phthalocyanines (Pc) to prevent infection by vaccinia virus in cell culture.Porphyrins were obtained from Midcentury Chemicals (Chicago, Illinois) or Frontier Scientific (Logan, Utah) and used as received. Porphyrin designations are as follows: PP, protoporphyrin IX; HP, hematoporphyrin IX; TPP, meso-tetraphenylporphine; TNapPS, sulfonated 5,10,15,20-tetra-nap