Virus inactivation in blood components by photoactive phenothiazine dyes

The virucidal properties of photoactive phenothiazine dyes, such as methylene blue, have been known approximately 70 years. The mechanism of virus inactivation involves binding of the dye to nucleic acid, absorption of light, generation of reactive oxygen species, guanine oxidation in the viral genome. The first practical research involving phenothiazine photosensitizers in transfusion medicine was sparked by efforts to prevent transmission of hepatitis from pooled plasma administered during the Korean War. During the last decade, methylene blue was used by some European countries for virus photoinactivation in fresh frozen plasma, whereas other phenothiazine derivatives with greater affinities for nucleic acids and capabilities to inactivate intracellular virus have been investigated for photochemical decontamination of red cell suspensions. The toxicity of methylene blue is well characterized; the drug has been used for many years to treat methemoglobinemia using concentrations orders of magnitude greater than those used for virus photoinactivation, and several filters have been developed to remove the dye from plasma. Future widespread use of phenothiazines for virus photoinactivation in blood components may depend on whether the risk inherent in their use is less than the residual risk from transfusion-transmitted viruses.