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1.
J Nanobiotechnology ; 20(1): 335, 2022 Jul 16.
Article in English | MEDLINE | ID: covidwho-1935529

ABSTRACT

BACKGROUND: Cytomegalovirus (CMV) pneumonia is a major cause of morbidity and mortality in immunodeficiency individuals, including transplant recipients and Acquired Immune Deficiency Syndrome patients. Antiviral drugs ganciclovir (GCV) and phosphonoformate (PFA) are first-line agents for pneumonia caused by herpesvirus infection. However, the therapy suffers from various limitations such as low efficiency, drug resistance, toxicity, and lack of specificity. METHODS: The antiviral drugs GCV and PFA were loaded into the pH-responsive nanoparticles fabricated by poly(lactic-co-glycolic acid) (PLGA) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and further coated with cell membranes derived from bone marrow mesenchymal stem cells to form artificial stem cells, namely MPDGP. We evaluated the viral suppression effects of MPDGP in vitro and in vivo. RESULTS: MPDGP showed significant inflammation tropism and efficient suppression of viral replication and virus infection-associated inflammation in the CMV-induced pneumonia model. The synergistic effects of the combination of viral DNA elongation inhibitor GCV and viral DNA polymerase inhibitor PFA on suppressing the inflammation efficiently. CONCLUSION: The present study develops a novel therapeutic intervention using artificial stem cells to deliver antiviral drugs at inflammatory sites, which shows great potential for the targeted treatment of pneumonia. To our best knowledge, we are the first to fabricate this kind of artificial stem cell to deliver antiviral drugs for pneumonia treatment.


Subject(s)
Antiviral Agents , Nanoparticle Drug Delivery System , Pneumonia/drug therapy , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Cytomegalovirus , Cytomegalovirus Infections/drug therapy , Fatty Acids, Monounsaturated/chemistry , Foscarnet/pharmacology , Foscarnet/therapeutic use , Ganciclovir/pharmacology , Ganciclovir/therapeutic use , Humans , Inflammation/drug therapy , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Quaternary Ammonium Compounds/chemistry , Stem Cells
2.
Molecules ; 26(19)2021 Sep 23.
Article in English | MEDLINE | ID: covidwho-1463764

ABSTRACT

Due to their large possibility of the structure modification, alkylammonium gemini surfactants are a rapidly growing class of compounds. They exhibit significant surface, aggregation and antimicrobial properties. Due to the fact that, in order to achieve the desired utility effect, the minimal concentration of compounds are used, they are in line with the principle of greenolution (green evolution) in chemistry. In this study, we present innovative synthesis of the homologous series of gemini surfactants modified at the spacer by the ether group, i.e., 3-oxa-1,5-pentane-bis(N-alkyl-N,N-dimethylammonium bromides). The critical micelle concentrations were determined. The minimal inhibitory concentrations of the synthesized compounds were determined against bacteria Escherichia coli ATCC 10536 and Staphylococcus aureus ATCC 6538; yeast Candida albicans ATCC 10231; and molds Aspergillus niger ATCC 16401 and Penicillium chrysogenum ATCC 60739. We also investigated the relationship between antimicrobial activity and alkyl chain length or the nature of the spacer. The obtained results indicate that the synthesized compounds are effective microbicides with a broad spectrum of biocidal activity.


Subject(s)
Anti-Infective Agents/pharmacology , Quaternary Ammonium Compounds/pharmacology , Surface-Active Agents/pharmacology , Anti-Infective Agents/chemistry , Aspergillus niger/drug effects , Candida albicans/drug effects , Escherichia coli/drug effects , Green Chemistry Technology , Micelles , Microbial Sensitivity Tests , Molecular Structure , Penicillium chrysogenum/drug effects , Quaternary Ammonium Compounds/chemistry , Staphylococcus aureus/drug effects , Surface-Active Agents/chemistry
4.
Int J Mol Sci ; 22(13)2021 Jun 24.
Article in English | MEDLINE | ID: covidwho-1304661

ABSTRACT

Quaternary ammonium compounds (QACs) belong to a well-known class of cationic biocides with a broad spectrum of antimicrobial activity. They are used as essential components in surfactants, personal hygiene products, cosmetics, softeners, dyes, biological dyes, antiseptics, and disinfectants. Simple but varied in their structure, QACs are divided into several subclasses: Mono-, bis-, multi-, and poly-derivatives. Since the beginning of the 20th century, a significant amount of work has been dedicated to the advancement of this class of biocides. Thus, more than 700 articles on QACs were published only in 2020, according to the modern literature. The structural variability and diverse biological activity of ionic liquids (ILs) make them highly prospective for developing new types of biocides. QACs and ILs bear a common key element in the molecular structure-quaternary positively charged nitrogen atoms within a cyclic or acyclic structural framework. The state-of-the-art research level and paramount demand in modern society recall the rapid development of a new generation of tunable antimicrobials. This review focuses on the main QACs exhibiting antimicrobial and antifungal properties, commercial products based on QACs, and the latest discoveries in QACs and ILs connected with biocide development.


Subject(s)
Disinfectants/chemistry , Disinfectants/pharmacology , Ionic Liquids/chemistry , Quaternary Ammonium Compounds/chemistry , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship
5.
Mol Pharm ; 18(6): 2448-2453, 2021 06 07.
Article in English | MEDLINE | ID: covidwho-1226403

ABSTRACT

Nanomedicine has demonstrated a substantial role in vaccine development against severe acute respiratory syndrome coronavirus (SARS-CoV-2 and COVID-19). Although nanomedicine-based vaccines have now been validated in millions of individuals worldwide in phase 4 and tracking of sex-disaggregated data on COVID-19 is ongoing, immune responses that underlie COVID-19 disease outcomes have not been clarified yet. A full understanding of sex-role effects on the response to nanomedicine products is essential to building an effective and unbiased response to the pandemic. Here, we exposed model lipid nanoparticles (LNPs) to whole blood of 18 healthy donors (10 females and 8 males) and used flow cytometry to measure cellular uptake by circulating leukocytes. Our results demonstrated significant differences in the uptake of LNP between male and female natural killer (NK) cells. The results of this proof-of-concept study show the importance of recipient sex as a critical factor which enables researchers to better consider sex in the development and administration of vaccines for safer and more-efficient sex-specific outcomes.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Nanoparticles/chemistry , SARS-CoV-2/immunology , COVID-19/epidemiology , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/chemistry , Drug Compounding/methods , Fatty Acids, Monounsaturated/chemistry , Female , Healthy Volunteers , Humans , Immunogenicity, Vaccine , Liposomes , Male , Pandemics/prevention & control , Quaternary Ammonium Compounds/chemistry , Sex Factors , Treatment Outcome
6.
Molecules ; 26(8)2021 Apr 12.
Article in English | MEDLINE | ID: covidwho-1178367

ABSTRACT

To determine whether quaternary ammonium (k21) binds to Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) spike protein via computational molecular docking simulations, the crystal structure of the SARS-CoV-2 spike receptor-binding domain complexed with ACE-2 (PDB ID: 6LZG) was downloaded from RCSB PD and prepared using Schrodinger 2019-4. The entry of SARS-CoV-2 inside humans is through lung tissues with a pH of 7.38-7.42. A two-dimensional structure of k-21 was drawn using the 2D-sketcher of Maestro 12.2 and trimmed of C18 alkyl chains from all four arms with the assumption that the core moiety k-21 was without C18. The immunogenic potential of k21/QA was conducted using the C-ImmSim server for a position-specific scoring matrix analyzing the human host immune system response. Therapeutic probability was shown using prediction models with negative and positive control drugs. Negative scores show that the binding of a quaternary ammonium compound with the spike protein's binding site is favorable. The drug molecule has a large Root Mean Square Deviation fluctuation due to the less complex geometry of the drug molecule, which is suggestive of a profound impact on the regular geometry of a viral protein. There is high concentration of Immunoglobulin M/Immunoglobulin G, which is concomitant of virus reduction. The proposed drug formulation based on quaternary ammonium to characterize affinity to the SARS-CoV-2 spike protein using simulation and computational immunological methods has shown promising findings.


Subject(s)
Drug Discovery , Quaternary Ammonium Compounds/metabolism , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Binding Sites , COVID-19/drug therapy , COVID-19/pathology , COVID-19/virology , Humans , Molecular Docking Simulation , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/metabolism , Quaternary Ammonium Compounds/chemistry , SARS-CoV-2/isolation & purification , Silanes/chemistry , Silanes/metabolism , Spike Glycoprotein, Coronavirus/chemistry
7.
Bioorg Med Chem Lett ; 36: 127808, 2021 03 15.
Article in English | MEDLINE | ID: covidwho-1034180

ABSTRACT

Commercial disinfectants are routinely used to decontaminate surfaces where microbes are expected and unwelcome. Several disinfectants contain quaternary ammonium salts, or "quats", all being derived from ammonium. Quaternary alkyl dimethyl benzyl ammonium chloride or bromide disinfectants are widely available. These compounds are effective in reducing or eliminating bacteria on contaminated nonporous surfaces. A unique benzyl derived boronium salt with strong detergent action has been developed. It demonstrated 4-8X greater antibacterial activity against 3 different bacteria when compared to an equal concentration of a commercial quant disinfectant solution containing alkyl dimethyl benzyl ammonium chloride and alkyl dimethyl ethylbenzyl ammonium chloride. Antibacterial effectiveness of each agent was determined by the minimum inhibitory concentration (MIC) method.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bromides/pharmacology , Disinfectants/pharmacology , Quaternary Ammonium Compounds/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Bromides/chemical synthesis , Bromides/chemistry , Disinfectants/chemical synthesis , Disinfectants/chemistry , Dose-Response Relationship, Drug , Escherichia coli/drug effects , Microbial Sensitivity Tests , Molecular Structure , Pseudomonas aeruginosa/drug effects , Quaternary Ammonium Compounds/chemical synthesis , Quaternary Ammonium Compounds/chemistry , Staphylococcus aureus/drug effects , Structure-Activity Relationship
8.
Sci Rep ; 11(1): 2418, 2021 01 28.
Article in English | MEDLINE | ID: covidwho-1054060

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is currently a global pandemic, and there are limited laboratory studies targeting pathogen resistance. This study aimed to investigate the effect of selected disinfection products and methods on the inactivation of SARS-CoV-2 in the laboratory. We used quantitative suspension testing to evaluate the effectiveness of the disinfectant/method. Available chlorine of 250 mg/L, 500 mg/L, and 1000 mg/L required 20 min, 5 min, and 0.5 min to inactivate SARS-CoV-2, respectively. A 600-fold dilution of 17% concentration of di-N-decyl dimethyl ammonium bromide (283 mg/L) and the same concentration of di-N-decyl dimethyl ammonium chloride required only 0.5 min to inactivate the virus efficiently. At 30% concentration for 1 min and 40% and above for 0.5 min, ethanol could efficiently inactivate SARS-CoV-2. Heat takes approximately 30 min at 56 °C, 10 min above 70 °C, or 5 min above 90 °C to inactivate the virus. The chlorinated disinfectants, Di-N-decyl dimethyl ammonium bromide/chloride, ethanol, and heat could effectively inactivate SARS-CoV-2 in the laboratory test. The response of SARS-CoV-2 to disinfectants is very similar to that of SARS-CoV.


Subject(s)
Disinfectants/pharmacology , Disinfection/methods , SARS-CoV-2/drug effects , Virus Inactivation/drug effects , COVID-19/prevention & control , COVID-19/virology , Chlorine/chemistry , Chlorine/pharmacology , Disinfectants/chemistry , Ethanol/chemistry , Ethanol/pharmacology , Humans , Pandemics/prevention & control , Quaternary Ammonium Compounds/chemistry , Quaternary Ammonium Compounds/pharmacology
9.
J Hosp Infect ; 108: 142-145, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-947282

ABSTRACT

BACKGROUND: SARS-CoV-2 is the virus responsible for the current global pandemic, COVID-19. Because this virus is novel, little is known about its sensitivity to disinfection. METHODS: We performed suspension tests against SARS-CoV-2 using three commercially available quaternary ammonium compound (Quat) disinfectants and one laboratory-made 0.2% benzalkonium chloride solution. FINDINGS: Three of the four formulations completely inactivated the virus within 15 s of contact, even in the presence of a soil load or when diluted in hard water. CONCLUSION: Quats rapidly inactivate SARS-CoV-2, making them potentially useful for controlling SARS-CoV-2 spread in hospitals and the community.


Subject(s)
Benzalkonium Compounds/pharmacology , COVID-19/prevention & control , Hand Sanitizers/pharmacology , Quaternary Ammonium Compounds/pharmacology , SARS-CoV-2/drug effects , Anti-Infective Agents, Local/chemistry , Anti-Infective Agents, Local/pharmacology , Benzalkonium Compounds/chemistry , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Disinfectants/chemistry , Disinfectants/classification , Disinfectants/pharmacology , Disinfection/methods , Hand Sanitizers/chemistry , Humans , Quaternary Ammonium Compounds/chemistry , SARS-CoV-2/genetics , SARS-CoV-2/growth & development , Treatment Outcome
10.
Cells ; 9(9)2020 09 05.
Article in English | MEDLINE | ID: covidwho-750713

ABSTRACT

Hybrid nanoparticles from lipidic and polymeric components were assembled to serve as vehicles for the transfection of messenger RNA (mRNA) using different portions of the cationic lipid DOTAP (1,2-Dioleoyl-3-trimethylammonium-propane) and the cationic biopolymer protamine as model systems. Two different sequential assembly approaches in comparison with a direct single-step protocol were applied, and molecular organization in correlation with biological activity of the resulting nanoparticle systems was investigated. Differences in the structure of the nanoparticles were revealed by thorough physicochemical characterization including small angle neutron scattering (SANS), small angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryo-TEM). All hybrid systems, combining lipid and polymer, displayed significantly increased transfection in comparison to lipid/mRNA and polymer/mRNA particles alone. For the hybrid nanoparticles, characteristic differences regarding the internal organization, release characteristics, and activity were determined depending on the assembly route. The systems with the highest transfection efficacy were characterized by a heterogenous internal organization, accompanied by facilitated release. Such a system could be best obtained by the single step protocol, starting with a lipid and polymer mixture for nanoparticle formation.


Subject(s)
Biopolymers/chemistry , Lipids/chemistry , Nanoparticles/chemistry , RNA, Messenger/metabolism , Transfection/methods , Animals , Cell Line , Fatty Acids, Monounsaturated/chemistry , Female , Heparin/chemistry , Humans , Mice , Mice, Inbred BALB C , Optical Imaging , Particle Size , Quaternary Ammonium Compounds/chemistry , RNA, Messenger/chemistry
11.
Ecotoxicol Environ Saf ; 206: 111116, 2020 Dec 15.
Article in English | MEDLINE | ID: covidwho-741186

ABSTRACT

Disinfectant quaternary ammonium compounds (Quats) have diverse uses in a variety of consumer and commercial products, particularly cleaning products. With the emergence of the COVID-19 pandemic, they have become a primary tool to inactivate the SARS-CoV-2 virus on surfaces. Disinfectant Quats have very low vapor pressure, and following the use phase of the products in which they are found, disposal is typically "down-the-drain" to wastewater treatment systems. Consequently, the potential for the greatest environmental effect is to the aquatic environment, from treated effluent, and potentially to soils, which might be amended with wastewater biosolids. Among the earliest used and still common disinfectant Quats are the alkyl dimethyl benzyl ammonium chloride (ADBAC) compounds and the dialkyl dimethyl ammonium chloride (DDAC) compounds. They are cationic surfactants often found in consumer and commercial surface cleaners. Because of their biocidal properties, disinfectant Quats are heavily regulated for human and environmental safety around the world. Consequently, there is a robust database of information regarding the ecological hazards and environmental fate of ADBAC and DDAC; however, some of the data presented are from unpublished studies that have been submitted to and reviewed by regulatory agencies (i.e., EPA and European Chemicals Agency) to support antimicrobial product registration. We summarize the available environmental fate data and the acute and chronic aquatic ecotoxicity data for freshwater species, including algae, invertebrates, fish, and plants using peer-reviewed literature and unpublished data submitted to and summarized by regulatory agencies. The lower limit of the range of the ecotoxicity data for disinfectant Quats tends to be lower than that for other surface active agents, such as nonionic or anionic surfactants. However, ecotoxicity is mitigated by environmental fate characteristics, the data for which we also summarize, including high biodegradability and a strong tendency to sorb to wastewater biosolids, sediment, and soil. As a result, disinfectant Quats are largely removed during wastewater treatment, and those residues discharged in treated effluent are likely to rapidly bind to suspended solids or sediments, thus mitigating their toxicity.


Subject(s)
Disinfectants/toxicity , Quaternary Ammonium Compounds/toxicity , Water Pollutants, Chemical/toxicity , Animals , Aquatic Organisms/drug effects , Biodegradation, Environmental , COVID-19/epidemiology , COVID-19/prevention & control , Disinfectants/chemistry , Disinfectants/pharmacology , Ecotoxicology , Humans , Pandemics/prevention & control , Quaternary Ammonium Compounds/chemistry , Quaternary Ammonium Compounds/pharmacology , Risk Assessment , SARS-CoV-2/drug effects , Waste Water/chemistry , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/pharmacology , Water Purification/methods
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