Targeting DNA and RNA in pathogens: Mode of action of amotosalen HCl

Blood products for transfusion may contain a wide variety of DNA- and RNA-based pathogens, including those for which there are no current tests, and they are vulnerable to emerging, unknown pathogens, thus compromising the safety of the products [1]. Amotosalen HCl (S-59), in combination with UVA light, has been developed for inactivation of a broad range of DNA- and RNA-based single- and double-stranded pathogens, viruses, bacteria, parasites, and leukocytes in platelet concentrates and plasma in a blood bank setting. Amotosalen is a heterocyclic psoralen compound that reacts by a three-step process with nucleic acids: (i) amotosalen intercalates into the double helix, (ii) upon illumination with long-wavelength ultraviolet light it covalently attaches to a single strand forming a monoadduct and (iii) additional illumination causes a photoreaction of the monoadduct forming a covalent interstrand or intrastrand crosslink. Inactivation rate is related to genome size. The amotosalen photochemical treatment process has been optimized to inactivate all significant pathogens in platelet concentrates as currently processed for transfusion in a blood bank setting, thus increasing the safety of the product.