Amustaline (S‐303) treatment inactivates high levels of Chikungunya virus in red‐blood‐cell components

Abstract

Chikungunya virus was previously shown to be inactivated by the PI technology using amotosalen and ultraviolet A light for the treatment of plasma and platelets. This new study demonstrates that S-303/GSH can inactivate high titres of CHIKV in RBCs.

Inactivation of SARS-CoV-2 in All Blood Components Using Amotosalen/Ultraviolet A Light and Amustaline/Glutathione Pathogen Reduction Technologies

“…AS-1 RBC received at BRI were pooled within blood type, if necessary, and adjusted, by weight (density is 1.06 g/mL) to approximately 360 mL. Each unit was spiked with SARS-CoV-2 stock virus at a 1:100 dilution (1% of total AS-1 RBC plus processing solution, GSH, and S-303; approximately 5.3 mL) and treated with the INTERCEPT Blood System for RBC as previously described [ 19 , 20 ], with some modifications. The INTERCEPT Blood System for RBC comprises an S-303 vial, a GSH vial, a trifurcated set with two 0.2-µm filters and a blind lead, and a processing set with three containers: a mixing bag containing a proprietary processing solution, an incubation bag, and a storage bag containing AS-1 additive solution.…”

“…Following sample collection, amustaline was added to the mixing bag and the RBC (containing processing solution, GSH, and amustaline) were transferred to the incubation bag. The unit, alongside the collected control samples, was stored at room temperature for 24 h. After incubation, an exchange step was performed as previously described [ 19 ] and a post-treatment test sample (Test, T = 24 h) was collected from each unit. This sample, along with one of the remaining control samples (untreated control, UT = 24 h) was stored at −80 °C until analysis.…”

“…Akin to A/UVA mode of action, treatment with amustaline irreversibly crosslinks nucleic acids, but is not dependent on UVA light ( Figure 1 ). S-303/GSH treatment has been shown to be effective at inactivating several viruses and protozoa, including chikungunya virus (CHIKV) [ 19 , 20 ], ZIKV [ 21 ], dengue virus (DENV) [ 22 ], and Plasmodium falciparum [ 23 ]. Previous studies have demonstrated that A/UVA treatment inactivates SARS-CoV and MERS-CoV, two relatives of SARS-CoV-2, in plasma and platelet concentrates (PC) [ 24 , 25 , 26 , 27 ].…”

Progress towards an appropriate pathogen reduction technology for whole blood in Africa

“…Amustaline has demonstrated robust inactivation of pathogens in RBCs (Table 2), including viruses [57][58][59][60][61][62][63][64], bacteria [63,[65][66][67][68] and protozoa [69,70] as well as residual donor leucocytes [71][72][73][74]. Due to its effectiveness against viral pathogens and donor leucocytes, the amustaline/GSH-based INTERCEPT system for RBCs has been proposed as an alternative to cytomegalovirus (CMV) serology and as a replacement for irradiation for the prevention of transfusion-associated graft-versus-host disease (TA-GVHD) [73].…”

Emerging Infectious Agents and Blood Safety in Latin America

“…In LATAM countries, with several social and health demands, it is debatable whether the resources to prevent a few TT-CHKV should not be invested in vector control, in order to benefit a larger number of inhabitants, including blood recipients that are off course also susceptible to mosquitoes’ bites in daily life outside blood transfusion settings. However, availability of, in development, arboviral multiplex NATs allowing for simultaneous detection of Dengue, Chikungunya, and Zika and/or pathogen reduction technologies acting on whole blood ( 43 ) or components, necessarily including red cells ( 44 ) may perhaps result in cost-effective measures to be implemented in endemic areas, home to the majority of the LATAM population.…”