Prevention of poxvirus infection by tetrapyrroles.
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.
Chen-Collins
Avril R M
AR
Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA. achenco@emory.edu
Dixon
Dabney W
DW
Vzorov
Andrei N
AN
Marzilli
Luigi G
LG
Compans
Richard W
RW
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D008027:Light; D011166:Porphyrins / Q000494:pharmacology / Q000627:therapeutic use; D011213:Poxviridae Infections / Q000517:prevention & control; D011524:Protoporphyrins / Q000494:pharmacology / Q000627:therapeutic use; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D014616:Vaccinia virus / Q000145:classification / Q000187:drug effects* / Q000502:physiology
D011166:Porphyrins; D011524:Protoporphyrins; D011758:Pyrroles; C409084:tetraphenylporphyrin; C017803:zinc protoporphyrin