Prevention of poxvirus infection by tetrapyrroles

Abstract

BackgroundPrevention 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.MethodsThe 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.ResultsExamples 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.ConclusionsPorphyrins 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.

The Cytoprotective Enzyme Heme Oxygenase-1 Suppresses Pseudorabies Virus Replication in vitro

“…Up-regulation of intracellular oxidative stress and downregulation of HO-1 in PRV-infected cells may indicate that PRV can induce oxidative stress in host cells and antagonizes the HO-1 pathway to facilite self-replication. Certain porphyrins and porphyrin derivatives possess virucidal effect against some other viruses, such as EBOV, HIV and MARV (Vzorov et al, 2002;Chen-Collins et al, 2003;Guo et al, 2011), thus the potential of virucidal effect of CoPP was evaluated. Co-incubation of PRV with CoPP had obvious, but not complete inhibitory effect on PRV proliferative property (Figures 6G,H), demonstrating certain virucidal activity.…”

Inactivation of Dengue and Yellow Fever viruses by heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX

“…In addition, the ability of these porphyrins to inactivate virus extends to other flaviviruses such as YFV. The antiviral activity of natural and synthetic porphyrins has been described for distinct viruses (Staudinger et al 1996;Vzorov et al 2002;Chen-Collins et al 2003;Benati et al 2009;Wen et al 2009;Cheng et al 2010;Hou et al 2010;Lehmann et al 2010;Zhu et al 2010;Guo et al 2011). The use of this class of molecules was proposed on PDI therapies (Pushpan et al 2002;Costa et al 2012).…”

“…It is also possible that porphyrins promote DENV particle instability and destruction. Porphyrin activity targeting directly the virus particles was demonstrated for other enveloped virus such as HIV, poxvirus and HBV (Vzorov et al 2002;Chen-Collins et al 2003;Guo et al 2011). Virucidal activity of chlorophyllide, an alkylated porphyrin, was demonstrated against HBV particles (Guo et al 2011).…”

The Cytoprotective Enzyme Heme Oxygenase-1 Suppresses Ebola Virus Replication

“…Certain porphyrins and porphyrin derivatives are broadly virucidal against a host of viruses, including EBOV and MARV (34)(35)(36). We therefore assessed the potential virucidal effects of CoPP.…”

“…Several porphyrins and porphyrin derivatives are virucidal, that is, able to reduce virus infectivity after direct contact with the virus (34)(35)(36). To determine whether CoPP affects EBOV virulence through this mechanism, 100 l of Ebola⌬VP30 virus (at 1 ϫ 10 6 focus-forming units [FFU]/ml) was diluted in medium containing CoPP at a final concentration of 15 M and incubated for 1 h at 37°C.…”