Binding Affinities of Commonly Employed Sensitizers of Viral Inactivation¶

Abstract

Methylene blue (MB), riboflavin (RB) and psoralen sensitizers (4′ aminomethyl‐4,5′,8‐trimethylpsoralen [AMT] and derivatives) are under study as sensitizers of viral inactivation of blood products such as plasma proteins, platelets and red cells, all of which lack genomic nucleic acid. To predict where these sensitizers accumulate in viruses and in cells, their relative affinities for calf thymus DNA, neutral and negatively charged phospholipids and albumin were determined by dialysis. MB has a strong affinity for nucleic acid and negatively charged phospholipid, but little affinity for albumin or neutral phospholipid. RB has modest affinity for nucleic acid and little affinity for albumin or either phospholipid. AMT has substantial affinity for nucleic acid, neutral and negatively charged phospholipids and albumin. Neither AMT nor RB binds to poly G, although MB has some affinity for this polymer. Evidence of association of RB with guanosine monophosphate, adenosine monophosphate and tryptophan methylester hydrochloride in PBS buffer in the presence and absence of formamide was obtained from nonlinear Stern–Volmer plots and shifts in the ground state absorption spectrum of RB.

Riboflavin and amotosalen photochemical treatments of platelet concentrates reduce thrombus formation kinetics in vitro

“…Furthermore, all photosensitizers produce reactive oxygen species (ROS), and these are by no means specific in their chemistry with the surrounding milieu. Moreover, photosensitizers not only partition to nucleic acids , but also to other biomolecules where reaction can occur.…”

Pathogen reduction treatment using riboflavin and ultraviolet light impairs platelet reactivity toward specific agonists in vitro

“…Second, overall cell damage is generated by reactive oxygen species, which are formed between riboflavin after UV illumination and oxygen in the PLT transfusion product. Finally, riboflavin intercalates into nucleic acid strands and oxidizes guanine bases upon illumination resulting in more damage to the cells 7‐9…”

Cell Technology for Cell Products

“…Several studies reported some vitamins as virus inactivators, e.g. riboflavin, present in our vitamins cocktail, was shown to selectively induce damage only to nucleic acids (Dardare and Platz, 2002) and probably this may explain the significant decrease on cell specific productivity, since AdV DNA damage might be occurring during AdV replication.…”