Influenza virus spreads via small particle aerosols, droplets and fomites, and since it can survive for a short time on surfaces, can be introduced into the nasal mucosa before it loses infectivity. The hypothiocyanite ion (OSCN-), product of the lactoperoxidase/H2O2/SCN- system of central airways, is emerging as an important molecule for innate defense mechanism against bacteria, fungi and viruses. Here we demonstrated that OSCN(-) displays virucidal activity in vitro against the A/H1N1 2009 pandemic influenza virus. The concentration required to inhibit viral replication by 50% was 2 μM when virus were challenged directly with OSCN- before cell inoculation. These values were even lower when inoculated cells were maintained in contact with enzyme free-OSCN- in the culture medium. The last experimental conditions better reflect those of tracheobronchial mucosa, where HOSCN/OSCN- is retained in the air-liquid interface and inactivates both the viruses approaching the epithelium from outside and those released from the inoculated cells after the replication cycle. Importantly no OSCN- cytotoxicity was observed in the cellular system employed. The lack of toxicity in humans and the absence of damage on surfaces of fomites suggest a potential use of OSCN- to avoid mucosal and environmental transmission of influenza virus. Since hypothiocyanite is normally present in human airways a low risk of viral resistance is envisaged. In vivo confirmatory studies are needed to evaluate the appropriate dose, regimen and formulation.
【저자키워드】 HIV, infection control, in vitro, RNA, DNA, rRT-PCR, respiratory syncytial virus, RSV, Disinfection, hemagglutinin, Human immunodeficiency virus, carbon dioxide, Ribonucleic acid, optical density, CO(2), Deoxyribonucleic acid, TPCK, fetal bovine serum, Nicotinamide adenine dinucleotide phosphate, Phosphate Buffered Saline, NADPH, TCID, hypothiocyanite, HA, MTT, MDCK, thiocyanate, neuraminidase, ATCC, DTNB, PBS, FBS, influenza treatment, MEM, SDS, NA, OD, lactoperoxidase, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, 5-thio-2-nitrobenzoic acid, 5′5 dithio-bis-2-nitrobenzoate, A/H1N1/2009, American tissue culture collection, DUOX, HOSCN, Influenza prophylaxis, LPO, Madin-Darby Canine kidney, Neuroaminidase, OSCN(−), OSCN(−) lactoperoxidase, SCN(−), TNB, dual oxidase, hypothiocyanite anion, hypothiocyanous acid, l-1-tosylamide-2-phenylethyl chloromethyl ketone, minimal essential medium, reverse transcriptase real-time polymerase chain reaction, sequence detection systems software, tissue culture infectious dose.,