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IARC Monographs on the Evaluation of... 1999
Review
Topics: Animals; Carcinogenicity Tests; Carcinogens; Humans; Mutagenicity Tests; Mutagens; Neoplasms, Experimental; Propiolactone; Salmonella typhimurium
PubMed: 10476379
DOI: No ID Found -
Journal of Virological Methods Jul 2023β-Propiolactone (BPL) is an organic compound widely used as an inactivating agent in vaccine development and production, for example for SARS-CoV, SARS-CoV-2 and... (Review)
Review
β-Propiolactone (BPL) is an organic compound widely used as an inactivating agent in vaccine development and production, for example for SARS-CoV, SARS-CoV-2 and Influenza viruses. Inactivation of pathogens by BPL is based on an irreversible alkylation of nucleic acids but also on acetylation and cross-linking between proteins, DNA or RNA. However, the protocols for BPL inactivation of viruses vary widely. Handling of infectious, enriched SARS-CoV-2 specimens and diagnostic samples from COVID-19 patients is recommended in biosafety level (BSL)- 3 or BSL-2 laboratories, respectively. We validated BPL inactivation of SARS-CoV-2 in saliva samples with the objective to use saliva from COVID-19 patients for training of scent dogs for the detection of SARS-CoV-2 positive individuals. Therefore, saliva samples and cell culture medium buffered with NaHCO (pH 8.3) were comparatively spiked with SARS-CoV-2 and inactivated with 0.1 % BPL for 1 h (h) or 71 h ( ± 1 h) at 2-8 °C, followed by hydrolysis of BPL at 37 °C for 1 or 2 h, converting BPL into non-toxic beta-hydroxy-propionic acid. SARS-CoV-2 inactivation was demonstrated by a titre reduction of up to 10^4 TCID/ml in the spiked samples for both inactivation periods using virus titration and virus isolation, respectively. The validated method was confirmed by successful inactivation of pathogens in saliva samples from COVID-19 patients. Furthermore, we reviewed the currently available literature on SARS-CoV-2 inactivation by BPL. Accordingly, BPL-inactivated, hydrolysed samples can be handled in a non-laboratory setting. Furthermore, our BPL inactivation protocols can be adapted to validation experiments with other pathogens.
Topics: Dogs; Animals; Propiolactone; Saliva; Odorants; COVID-19; Virus Inactivation; SARS-CoV-2; Viruses
PubMed: 37068591
DOI: 10.1016/j.jviromet.2023.114733 -
Chemical Research in Toxicology Mar 2020The discovery that β-propiolactone (BPL), once a commercially important chemical, causes various tumors in experimental animals has led to a significant decrease in its...
The discovery that β-propiolactone (BPL), once a commercially important chemical, causes various tumors in experimental animals has led to a significant decrease in its use. However, owing to its efficacy this possible human carcinogen remains to be utilized in vaccines for inactivation of viruses. The focus of the current study was to uncover the mechanisms of β-propiolactone reactions with both nucleobases and glutathione (GSH) through computer simulations based on quantum chemical methods. Our results, in accordance with in vitro studies, show that among all nucleobases guanine most readily forms adducts with BPL through S2 reaction mechanism. Acquired activation energies with incorporated solvent effects reveal that alkylation represents an energetically more favorable reaction than acylation for all nucleobases. Comparison of activation free energies of glutathione and guanine reactions with BPL suggest that glutathione may represent an efficient natural scavenger of BPL. Therefore, glutathione present in the organism may provide protection to the DNA and thus prevent BPL's genotoxicity, mutagenicity, and possibly even carcinogenicity.
Topics: Carcinogenesis; Density Functional Theory; Humans; Models, Molecular; Molecular Structure; Propiolactone; Thermodynamics
PubMed: 32056425
DOI: 10.1021/acs.chemrestox.9b00389 -
Report on Carcinogens : Carcinogen... 2011
Topics: Animals; Carcinogens; Disinfectants; Female; Humans; Male; Neoplasms; Occupational Exposure; Propiolactone
PubMed: 21863089
DOI: No ID Found -
Report on Carcinogens : Carcinogen... 2004
Topics: Animals; Carcinogenicity Tests; Carcinogens; Disinfectants; Female; Government Regulation; Guidelines as Topic; Humans; Male; Mice; Models, Biological; Occupational Exposure; Propiolactone; Rats; United States
PubMed: 21105255
DOI: No ID Found -
Report on Carcinogens : Carcinogen... 2002
Topics: Animals; Carcinogens; Environmental Exposure; Government Regulation; Humans; Propiolactone; United States
PubMed: 15334719
DOI: No ID Found -
Die Pharmazie Mar 1973
Review
Topics: Air Microbiology; Disinfectants; Lactones; Propionates; Sterilization
PubMed: 4573487
DOI: No ID Found -
Mutation Research 1977
Review
Topics: Animals; Carcinogens; Cells, Cultured; Chromosome Aberrations; Coliphages; DNA; DNA Repair; Drosophila; Escherichia coli; Lactones; Macromolecular Substances; Mutagens; Neurospora crassa; Propiolactone; Saccharomyces cerevisiae; Salmonella typhimurium
PubMed: 142920
DOI: 10.1016/0165-1110(77)90007-0 -
Microscopy Research and Technique Feb 2022The severe COVID-19 pandemic drives the research toward the SARS-CoV-2 virion structure and the possible therapies against it. Here, we characterized the...
The severe COVID-19 pandemic drives the research toward the SARS-CoV-2 virion structure and the possible therapies against it. Here, we characterized the β-propiolactone inactivated SARS-CoV-2 virions using transmission electron microscopy (TEM) and atomic force microscopy (AFM). We compared the SARS-CoV-2 samples purified by two consecutive chromatographic procedures (size exclusion chromatography [SEC], followed by ion-exchange chromatography [IEC]) with samples purified by ultracentrifugation. The samples prepared using SEC and IEC retained more spikes on the surface than the ones prepared using ultracentrifugation, as confirmed by TEM and AFM. TEM showed that the spike (S) proteins were in the pre-fusion conformation. Notably, the S proteins could be recognized by specific monoclonal antibodies. Analytical TEM showed that the inactivated virions retained nucleic acid. Altogether, we demonstrated that the inactivated SARS-CoV-2 virions retain the structural features of native viruses and provide a prospective vaccine candidate.
Topics: Animals; COVID-19; Chlorocebus aethiops; Humans; Pandemics; Propiolactone; SARS-CoV-2; Vaccines, Inactivated; Vero Cells
PubMed: 34498784
DOI: 10.1002/jemt.23931 -
Current Studies in Hematology and Blood... 1989A combined treatment of plasma or plasma derivatives by beta-propiolactone (beta-PL)/UV irradiation is in use at Biotest for the preparation of the virus-safe,... (Review)
Review
A combined treatment of plasma or plasma derivatives by beta-propiolactone (beta-PL)/UV irradiation is in use at Biotest for the preparation of the virus-safe, stabilized serum (Biseko) and coagulation factor concentrates. The efficacy of this sterilization procedure has been demonstrated for HAV (greater than 8.2 log10), HBV (6.9 log10), NANBHV (greater than 4.5 log10) and HIV (greater than 6.0 log10). The methods used in these studies (titration in chimpanzees or cell cultures) are not applicable in routine monitoring of sterilization processes. We therefore developed a test system using four types of bacteriophages: phi X174, phi e, Kappa and f2. Using these bacteriophages in 88 single tests, sterilization efficacy was regularly monitored during the period from 1981 to 1986. The four types of bacteriophages showed, on average, an inactivation rate of 6.7 log10, independent of size or genome structure. This inactivation is in the range of the inactivation of the relevant pathogenic virus, HBV, by beta-PL/UV. It was shown that under the production conditions of Intraglobin and the other Biotest immunoglobulin preparations, beta-PL (without UV) is as virucidal as the combination of beta-PL/UV in plasma or cryo-poor plasma.
Topics: Animals; Blood Component Removal; Chemical Fractionation; HIV; Hepatitis Viruses; Humans; Lactones; Plasma; Propiolactone; Sterilization; Ultraviolet Rays
PubMed: 2642784
DOI: 10.1159/000416562