Amustaline (S-303) treatment inactivates high levels of Zika virus in red blood cell components.
The potential for Zika virus (ZIKV) transfusion-transmission (TT) has been demonstrated in French Polynesia and Brazil. Pathogen inactivation (PI) of blood products is a proactive strategy to inactivate TT pathogens including arboviruses. Inactivation of West Nile, dengue, Zika, and chikungunya viruses was previously demonstrated by photochemical treatment with amotosalen and ultraviolet A (UVA) illumination. In this study, we evaluated ZIKV inactivation in red blood cell (RBC) components by a chemical approach that uses amustaline (S-303) and glutathione (GSH).



RBC components were spiked with a high titer of ZIKV. Viral titers (infectivity) and ZIKV RNA loads (reverse transcription-polymerase chain reaction) were measured in spiked RBCs before and after S-303 and GSH treatment and confirmed using repetitive passages in cell culture. A mock-treated arm validated the approach by demonstrating stability of the virus (infectivity and RNA load) during the process.



The mean ZIKV infectivity titer and RNA load in RBCs were 5.99 ± 0.2 log 50% tissue culture infectious dose (TCID50)/mL and 7.75 ± 0.16 log genomic equivalents/mL before inactivation. No infectivity was detected immediately after S-303 and GSH treatment and after five serial passages in cell culture.



Complete ZIKV inactivation of more than 5.99 log TCID50/mL in RBCs was achieved using S-303 and GSH at levels higher than those found in asymptomatic ZIKV-infected blood donors. Therefore, the S-303 and GSH PI system is promising for mitigating the risk of ZIKV TT.
Cerus Corporation, Concord, California.
Andrew
A
Laughhunn
Cerus Corporation, Concord, California.
Felicia
F
Santa Maria
Centre de Transfusion Sanguine de la Polynésie Française, Hôpital du Taaone.
Julien
J
Broult
Cerus Corporation, Concord, California.
Marion C
MC
Lanteri
Cerus Corporation, Concord, California.
Adonis
A
Stassinopoulos
Pôle de Recherche et de Veille sur les Maladies Infectieuses Émergentes, Institut Louis Malardé, Tahiti, Polynésie Française.
Didier
D
Musso
Pôle de Recherche et de Veille sur les Maladies Infectieuses Émergentes, Institut Louis Malardé, Tahiti, Polynésie Française.
Maite
M
Aubry
D000166:Acridines / Q000737:chemistry / Q000494:pharmacology*; D004203:Disinfection / Q000379:methods*; D004912:Erythrocytes / Q000821:virology*; D005260:Female; D006801:Humans; D008297:Male; D009588:Nitrogen Mustard Compounds / Q000737:chemistry / Q000494:pharmacology*; D012367:RNA, Viral / Q000097:blood*; D038301:Virus Inactivation; D000071244:Zika Virus
C506266:(N,N-bis(2-chloroethyl))-2-aminoethyl-3-((acridin-9-yl)amino)propionate; D000166:Acridines; D009588:Nitrogen Mustard Compounds; D012367:RNA, Viral