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1.
J Antibiot (Tokyo) ; 75(6): 321-332, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1878523

ABSTRACT

Staphylococcus aureus is one of the most dangerous pathogens commonly associated with high levels of morbidity and mortality. Sortase A is considered as a promising molecular target for the development of antistaphylococcal agents. Using hybrid virtual screening approach and FRET analysis, we have identified five compounds able to decrease the activity of sortase A by more than 50% at the concentration of 200 µM. The most promising compound was 2-(2-amino-3-chloro-benzoylamino)-benzoic acid which was able to inhibit S. aureus sortase A at the IC50 value of 59.7 µM. This compound was selective toward sortase A compared to other four cysteine proteases - cathepsin L, cathepsin B, rhodesain, and the SARS-CoV2 main protease. Microscale thermophoresis experiments confirmed that this compound bound sortase A with KD value of 189 µM. Antibacterial and antibiofilm assays also confirmed high specificity of the hit compound against two standard and three wild-type, S. aureus hospital infection isolates. The effect of the compound on biofilms produced by two S. aureus ATCC strains was also observed suggesting that the compound reduced biofilm formation by changing the biofilm structure and thickness.


Subject(s)
COVID-19 , Staphylococcal Infections , Aminoacyltransferases , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/metabolism , Biofilms , Cysteine Endopeptidases , Humans , Microbial Sensitivity Tests , RNA, Viral/pharmacology , SARS-CoV-2 , Staphylococcus aureus
2.
ACS Appl Mater Interfaces ; 14(21): 24850-24855, 2022 Jun 01.
Article in English | MEDLINE | ID: covidwho-1852371

ABSTRACT

The demand for improved indoor air quality, especially during the pandemic of Covid-19, has led to renewed interest in antiviral and antibacterial air-conditioning systems. Here, air filters of vehicles made of nonwoven polyester filter media were sonochemically coated with CuO nanoparticles by a roll-to-roll coating method. The product, aimed at providing commuters with high air quality, showed good stability and mechanical properties and potent activity against Escherichia coli and Staphylococcus aureus bacteria, H1N1 influenza, and two SARS-CoV-2 variants. The filtering properties of a coated filter were tested, and they were similar to those of the uncoated filter. Leaching tests as a function of airflow were conducted, and the main outcome was that the coating was stable and particles were not detached from the coated media. Extension to other air-conditioning systems was straightforward.


Subject(s)
Air Filters , COVID-19 , Influenza A Virus, H1N1 Subtype , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Automobiles , Copper , Escherichia coli , Humans , SARS-CoV-2
3.
Sci Rep ; 12(1): 7193, 2022 05 03.
Article in English | MEDLINE | ID: covidwho-1821611

ABSTRACT

The current Coronavirus Disease 19 (COVID-19) pandemic has exemplified the need for simple and efficient prevention strategies that can be rapidly implemented to mitigate infection risks. Various surfaces have a long history of antimicrobial properties and are well described for the prevention of bacterial infections. However, their effect on many viruses has not been studied in depth. In the context of COVID-19, several surfaces, including copper (Cu) and silver (Ag) coatings have been described as efficient antiviral measures that can easily be implemented to slow viral transmission. In this study, we detected antiviral properties against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) on surfaces, which were coated with Cu by magnetron sputtering as thin Cu films or as Cu/Ag ultrathin bimetallic nanopatches. However, no effect of Ag on viral titers was observed, in clear contrast to its well-known antibacterial properties. Further enhancement of Ag ion release kinetics based on an electrochemical sacrificial anode mechanism did not increase antiviral activity. These results clearly demonstrate that Cu and Ag thin film systems display significant differences in antiviral and antibacterial properties which need to be considered upon implementation.


Subject(s)
COVID-19 , Silver , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antiviral Agents/pharmacology , Copper/chemistry , Copper/pharmacology , Humans , SARS-CoV-2 , Silver/chemistry , Silver/pharmacology
4.
Int J Mol Sci ; 23(7)2022 Mar 25.
Article in English | MEDLINE | ID: covidwho-1785729

ABSTRACT

The development of affordable, effective, and environmentally friendly barrier fabrics is a current goal in antimicrobial textile development. The discovery of new routes to achieve non-toxic naturally occurring molecules with antimicrobial activity is of interest in the development of materials that promote wound healing, improve hygiene, and offer protection against nosocomial infection. Highly cleaned and sterile unbleached cotton has constituents that produce hydrogen peroxide at levels commensurate with those that favor cell signaling in wound healing. Here, we show the antimicrobial and antiviral properties of spunlaced griege cotton-containing nonwovens treated with ascorbic acid formulations. The mechanism of action occurs through the promotion of enhanced hydrogen peroxide activity. The levels of hydrogen peroxide activity afford antimicrobial activity against Gram-negative and Gram-positive bacteria and antiviral activity against MS2 bacteriophages. Spun-bond nonwoven unbleached cotton was treated with ascorbic acid using traditional pad-dry-cure methods. An assessment of antibacterial and antiviral activity against Staphylococcus aureus, Klebsiella pneumoniae, and MS2 bacteriophages with the AATCC 100 test method showed a 99.99% inhibitory activity. An approach to the covalent attachment of ascorbic to cellulose through citric acid crosslinking chemistry is also discussed. Thus, a simple, low-cost approach to antimicrobial and antiviral cotton-based nonwovens applicable to dressings, nosocomial barrier fabrics, and face masks can be adopted by combining ascorbic acid with spunlace greige cotton nonwoven fabrics.


Subject(s)
Anti-Infective Agents , Cotton Fiber , Adjuvants, Pharmaceutic , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Antiviral Agents , Ascorbic Acid/pharmacology , Gossypium , Hydrogen Peroxide , Textiles
5.
Sci Total Environ ; 820: 153049, 2022 May 10.
Article in English | MEDLINE | ID: covidwho-1730084

ABSTRACT

With the outbreak and widespread of the COVID-19 pandemic, large numbers of disposable face masks (DFMs) were abandoned in the environment. This study first investigated the sorption and desorption behaviors of four antibiotics (tetracycline (TC), ciprofloxacin (CIP), sulfamethoxazole (SMX), and triclosan (TCS)) on DFMs in the freshwater and seawater. It was found that the antibiotics in the freshwater exhibited relatively higher sorption and desorption capacities on the DFMs than those in the seawater. Here the antibiotics sorption processes were greatly related to their zwitterion species while the effect of salinity on the sorption processes was negligible. However, the desorption processes were jointly dominated by solution pH and salinity, with greater desorption capacities at lower pH values and salinity. Interestingly, we found that the distribution coefficient (Kd) of TCS (0.3947 L/g) and SMX (0.0399 L/g) on DFMs was higher than those on some microplastics in freshwater systems. The sorption affinity of the antibiotics onto the DFMs followed the order of TCS > SMX > CIP > TC, which was positively correlated with octanol-water partition coefficient (log Kow) of the antibiotics. Besides, the sorption processes of the antibiotics onto the DFMs were mainly predominated by film diffusion and partitioning mechanism. Overall, hydrophobic interaction regulated the antibiotics sorption processes. These findings would help to evaluate the environmental behavior of DFMs and to provide the analytical framework of their role in the transport of other pollutants.


Subject(s)
COVID-19 , Water Pollutants, Chemical , Adsorption , Anti-Bacterial Agents/chemistry , Fresh Water/chemistry , Humans , Masks , Pandemics , Plastics/chemistry , Seawater/chemistry , Water Pollutants, Chemical/analysis
6.
ChemistryOpen ; 11(2): e202100260, 2022 02.
Article in English | MEDLINE | ID: covidwho-1704277

ABSTRACT

Cationic conjugated oligoelectrolytes (COEs) are a class of compounds that can be tailored to achieve relevant in vitro antimicrobial properties with relatively low cytotoxicity against mammalian cells. Three distyrylbenzene-based COEs were designed containing amide functional groups on the side chains. Their properties were compared to two representative COEs with only quaternary ammonium groups. The optimal compound, COE2-3C-C3-Apropyl, has an antimicrobial efficacy against Escherichia coli with an MIC=2 µg mL-1 , even in the presence of human serum albumin low cytotoxicity (IC50 =740 µg mL-1 ) and minimal hemolytic activity. Moreover, we find that amide groups increase interactions between COEs and a bacterial lipid mimic based on calcein leakage assay and allow COEs to readily permeabilize the cytoplasmic membrane of E. coli. These findings suggest that hydrogen bond forming moieties can be further applied in the molecular design of antimicrobial COEs to further improve their selectivity towards bacteria.


Subject(s)
Anti-Infective Agents , Escherichia coli , Amides/analysis , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/analysis , Anti-Infective Agents/chemistry , Bacteria , Cell Membrane , Gram-Negative Bacteria , Humans , Mammals
7.
Molecules ; 27(4)2022 Feb 13.
Article in English | MEDLINE | ID: covidwho-1686904

ABSTRACT

(1) Background: Acne is a widespread skin disease, especially among adolescents. Following the COVID-19 pandemic and the use of masks, the problem has been affecting a greater number of people, and the attention of the skin care beauty routine cosmetics has been focused on the "Maskne", caused by the sebum excretion rate (SER) that stimulates microbial proliferation. (2) Methods: the present study was focused on the rheological characterization and quality assurance of the preservative system of an anti-acne serum. The biological effectiveness (cytotoxicity-skin and eye irritation-antimicrobial, biofilm eradication and anti-inflammatory activity) was evaluated in a monolayer cell line of keratinocytes (HaCaT) and on 3D models (reconstructed human epidermis, RHE and human reconstructed corneal epithelium, HCE). The Cutibacterium acnes, as the most relevant acne-inducing bacterium, is chosen as a pro-inflammatory stimulus and to evaluate the antimicrobial activity of the serum. (3) Results and Conclusions: Rheology allows to simulate serum behavior at rest, extrusion and application, so the serum could be defined as having a solid-like behavior and being pseudoplastic. The preservative system is in compliance with the criteria of the reference standard. Biological effectiveness evaluation shows non-cytotoxic and irritant behavior with a good antimicrobial and anti-inflammatory activity of the formulation, supporting the effectiveness of the serum for acne-prone skin treatment.


Subject(s)
Acne Vulgaris/drug therapy , Anti-Bacterial Agents , Biofilms/drug effects , COVID-19 , Cosmeceuticals , Pandemics , Propionibacteriaceae/physiology , SARS-CoV-2 , Acne Vulgaris/microbiology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Cell Line, Transformed , Cosmeceuticals/chemistry , Cosmeceuticals/pharmacology , Humans
8.
Mar Drugs ; 20(1)2022 Jan 11.
Article in English | MEDLINE | ID: covidwho-1667236

ABSTRACT

The underexplored biodiversity of seaweeds has recently drawn great attention from researchers to find the bioactive compounds that might contribute to the growth of the blue economy. In this study, we aimed to explore the effect of seasonal growth (from May to September) on the in vitro antioxidant (FRAP, DPPH, and ORAC) and antimicrobial effects (MIC and MBC) of Cystoseira compressa collected in the Central Adriatic Sea. Algal compounds were analyzed by UPLC-PDA-ESI-QTOF, and TPC and TTC were determined. Fatty acids, among which oleic acid, palmitoleic acid, and palmitic acid were the dominant compounds in samples. The highest TPC, TTC and FRAP were obtained for June extract, 83.4 ± 4.0 mg GAE/g, 8.8 ± 0.8 mg CE/g and 2.7 ± 0.1 mM TE, respectively. The highest ORAC value of 72.1 ± 1.2 µM TE was obtained for the August samples, and all samples showed extremely high free radical scavenging activity and DPPH inhibition (>80%). The MIC and MBC results showed the best antibacterial activity for the June, July and August samples, when sea temperature was the highest, against Listeria monocytogenes, Staphylococcus aureus, and Salmonella enteritidis. The results show C. compressa as a potential species for the industrial production of nutraceuticals or functional food ingredients.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antioxidants/pharmacology , Plant Extracts/pharmacology , Seaweed , Animals , Anti-Bacterial Agents/chemistry , Antioxidants/chemistry , Aquatic Organisms , Biphenyl Compounds , Mediterranean Sea , Microbial Sensitivity Tests , Picrates , Plant Extracts/chemistry , Salmonella enteritidis/drug effects , Seasons , Staphylococcus aureus/drug effects
9.
J Nanobiotechnology ; 19(1): 458, 2021 Dec 28.
Article in English | MEDLINE | ID: covidwho-1577211

ABSTRACT

Bio-inspired Topographically Mediated Surfaces (TMSs) based on high aspect ratio nanostructures have recently been attracting significant attention due to their pronounced antimicrobial properties by mechanically disrupting cellular processes. However, scalability of such surfaces is often greatly limited, as most of them rely on micro/nanoscale fabrication techniques. In this report, a cost-effective, scalable, and versatile approach of utilizing diamond nanotechnology for producing TMSs, and using them for limiting the spread of emerging infectious diseases, is introduced. Specifically, diamond-based nanostructured coatings are synthesized in a single-step fabrication process with a densely packed, needle- or spike-like morphology. The antimicrobial proprieties of the diamond nanospike surface are qualitatively and quantitatively analyzed and compared to other surfaces including copper, silicon, and even other diamond surfaces without the nanostructuring. This surface is found to have superior biocidal activity, which is confirmed via scanning electron microscopy images showing definite and widespread destruction of E. coli cells on the diamond nanospike surface. Consistent antimicrobial behavior is also observed on a sample prepared seven years prior to testing date.


Subject(s)
Anti-Bacterial Agents/chemistry , Coated Materials, Biocompatible/chemistry , Diamond/chemistry , Nanostructures/chemistry , Anti-Bacterial Agents/pharmacology , Coated Materials, Biocompatible/pharmacology , Copper/chemistry , Copper/pharmacology , Diamond/pharmacology , Escherichia coli/drug effects , Escherichia coli/growth & development , Nanostructures/ultrastructure , Nanotechnology , Surface Properties
10.
Science ; 372(6547): 1169-1175, 2021 06 11.
Article in English | MEDLINE | ID: covidwho-1583231

ABSTRACT

Emergent resistance to all clinical antibiotics calls for the next generation of therapeutics. Here we report an effective antimicrobial strategy targeting the bacterial hydrogen sulfide (H2S)-mediated defense system. We identified cystathionine γ-lyase (CSE) as the primary generator of H2S in two major human pathogens, Staphylococcus aureus and Pseudomonas aeruginosa, and discovered small molecules that inhibit bacterial CSE. These inhibitors potentiate bactericidal antibiotics against both pathogens in vitro and in mouse models of infection. CSE inhibitors also suppress bacterial tolerance, disrupting biofilm formation and substantially reducing the number of persister bacteria that survive antibiotic treatment. Our results establish bacterial H2S as a multifunctional defense factor and CSE as a drug target for versatile antibiotic enhancers.


Subject(s)
Anti-Bacterial Agents/pharmacology , Cystathionine gamma-Lyase/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Hydrogen Sulfide/metabolism , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/metabolism , Biofilms , Crystallography, X-Ray , Cystathionine gamma-Lyase/chemistry , Cystathionine gamma-Lyase/genetics , Cystathionine gamma-Lyase/metabolism , Drug Discovery , Drug Resistance, Bacterial , Drug Synergism , Drug Tolerance , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/metabolism , Mice , Microbial Sensitivity Tests , Models, Molecular , Molecular Docking Simulation , Molecular Structure , Pseudomonas Infections/drug therapy , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/enzymology , Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/growth & development , Small Molecule Libraries/chemistry , Small Molecule Libraries/metabolism , Small Molecule Libraries/pharmacology , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Staphylococcus aureus/enzymology , Staphylococcus aureus/genetics , Staphylococcus aureus/growth & development
11.
Int J Mol Sci ; 22(24)2021 Dec 14.
Article in English | MEDLINE | ID: covidwho-1572494

ABSTRACT

Low density polyethylene (LDPE) films covered with active coatings containing mixtures of rosemary, raspberry, and pomegranate CO2 extracts were found to be active against selected bacterial strains that may extend the shelf life of food products. The coatings also offer antiviral activity, due to their influence on the activity of Φ6 bacteriophage, selected as a surrogate for SARS-CoV-2 particles. The mixture of these extracts could be incorporated into a polymer matrix to obtain a foil with antibacterial and antiviral properties. The initial goal of this work was to obtain active LDPE films containing a mixture of CO2 extracts of the aforementioned plants, incorporated into an LDPE matrix via an extrusion process. The second aim of this study was to demonstrate the antibacterial properties of the active films against Gram-positive and Gram-negative bacteria, and to determine the antiviral effect of the modified material on Φ6 bacteriophage. In addition, an analysis was made on the influence of the active mixture on the polymer physicochemical features, e.g., mechanical and thermal properties, as well as its color and transparency. The results of this research indicated that the LDPE film containing a mixture of raspberry, rosemary, and pomegranate CO2 extracts incorporated into an LDPE matrix inhibited the growth of Staphylococcus aureus. This film was also found to be active against Bacillus subtilis. This modified film did not inhibit the growth of Escherichia coli and Pseudomonas syringae cells; however, their number decreased significantly. The LDPE active film was also found to be active against Φ6 particles, meaning that the film had antiviral properties. The incorporation of the mixture of CO2 extracts into the polymer matrix affected its mechanical properties. It was observed that parameters describing mechanical properties decreased, although did not affect the transition of LDPE significantly. Additionally, the modified film exhibited barrier properties towards UV radiation. Modified PE/CO2 extracts films could be applied as a functional food packaging material with antibacterial and antiviral properties.


Subject(s)
Food Packaging/methods , Plant Extracts/pharmacology , Polyethylene/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Bacteriophage phi 6/drug effects , Biofilms , Chitosan/chemistry , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Plant Extracts/chemistry , Polyethylene/pharmacology , Polymers/chemistry , Pomegranate , Rosmarinus/chemistry , Rubus , SARS-CoV-2/drug effects
12.
Int J Mol Sci ; 22(22)2021 Nov 21.
Article in English | MEDLINE | ID: covidwho-1534090

ABSTRACT

Twenty lupane type A-ring azepano-triterpenoids were synthesized from betulin and its related derivatives and their antitubercular activity against Mycobacterium tuberculosis, mono-resistant MTB strains, and nontuberculous strains Mycobacterium abscessus and Mycobacterium avium were investigated in the framework of AToMIc (Anti-mycobacterial Target or Mechanism Identification Contract) realized by the Division of Microbiology and Infectious Diseases, NIAID, National Institute of Health. Of all the tested triterpenoids, 17 compounds showed antitubercular activity and 6 compounds were highly active on the H37Rv wild strain (with MIC 0.5 µM for compound 7), out of which 4 derivatives also emerged as highly active compounds on the three mono-resistant MTB strains. Molecular docking corroborated with a machine learning drug-drug similarity algorithm revealed that azepano-triterpenoids have a rifampicin-like antitubercular activity, with compound 7 scoring the highest as a potential M. tuberculosis RNAP potential inhibitor. FIC testing demonstrated an additive effect of compound 7 when combined with rifampin, isoniazid and ethambutol. Most compounds were highly active against M. avium with compound 14 recording the same MIC value as the control rifampicin (0.0625 µM). The antitubercular ex vivo effectiveness of the tested compounds on THP-1 infected macrophages is correlated with their increased cell permeability. The tested triterpenoids also exhibit low cytotoxicity and do not induce antibacterial resistance in MTB strains.


Subject(s)
Antitubercular Agents/chemistry , Mycobacterium tuberculosis/drug effects , Triterpenes/chemistry , Tuberculosis/drug therapy , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antitubercular Agents/pharmacology , DNA-Directed RNA Polymerases/antagonists & inhibitors , DNA-Directed RNA Polymerases/genetics , Drug Design , Drug Resistance, Bacterial/genetics , Humans , Molecular Docking Simulation , Molecular Structure , Mycobacterium tuberculosis/pathogenicity , Rifampin/pharmacology , Triterpenes/pharmacology , Tuberculosis/genetics , Tuberculosis/microbiology
13.
Nucleic Acids Res ; 50(D1): D1282-D1294, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1493886

ABSTRACT

The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb; www.guidetopharmacology.org) is an open-access, expert-curated database of molecular interactions between ligands and their targets. We describe expansion in content over nine database releases made during the last two years, which has focussed on three main areas of infection. The COVID-19 pandemic continues to have a major impact on health worldwide. GtoPdb has sought to support the wider research community to understand the pharmacology of emerging drug targets for SARS-CoV-2 as well as potential targets in the host to block viral entry and reduce the adverse effects of infection in patients with COVID-19. We describe how the database rapidly evolved to include a new family of Coronavirus proteins. Malaria remains a global threat to half the population of the world. Our database content continues to be enhanced through our collaboration with Medicines for Malaria Venture (MMV) on the IUPHAR/MMV Guide to MALARIA PHARMACOLOGY (www.guidetomalariapharmacology.org). Antibiotic resistance is also a growing threat to global health. In response, we have extended our coverage of antibacterials in partnership with AntibioticDB.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antimalarials/pharmacology , Antiviral Agents/pharmacology , COVID-19/drug therapy , Anti-Bacterial Agents/chemistry , COVID-19/etiology , Data Curation , Databases, Pharmaceutical , Humans , Ligands , Malaria/drug therapy , Malaria/metabolism , User-Computer Interface , Viral Proteins/chemistry , Viral Proteins/metabolism
14.
Carbohydr Polym ; 273: 118605, 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1370153

ABSTRACT

Advanced biomaterials provide an interesting and versatile platform to implement new and more effective strategies to fight bacterial infections. Chitosan is one of these biopolymers and possesses relevant features for biomedical applications. Here we synthesized nanoparticles of chitosan derivatized with diethylaminoethyl groups (ChiDENPs) to emulate the choline residues in the pneumococcal cell wall and act as ligands for choline-binding proteins (CBPs). Firstly, we assessed the ability of diethylaminoethyl (DEAE) to sequester the CBPs present in the bacterial surface, thus promoting chain formation. Secondly, the CBP-binding ability of ChiDENPs was purposed to encapsulate a bio-active molecule, the antimicrobial enzyme Cpl-711 (ChiDENPs-711), with improved stability over non-derivatized chitosan. The enzyme-loaded system released more than 90% of the active enzybiotic in ≈ 2 h, above the usual in vivo half-life of this kind of enzymes. Therefore, ChiDENPs provide a promising platform for the controlled release of CBP-enzybiotics in biological contexts.


Subject(s)
Anti-Bacterial Agents/pharmacology , Biomimetic Materials/chemistry , Chitosan/analogs & derivatives , Drug Carriers/chemistry , Endopeptidases/pharmacology , Nanoparticles/chemistry , A549 Cells , Anti-Bacterial Agents/chemistry , Bacterial Proteins/metabolism , Biomimetic Materials/metabolism , Chitosan/chemistry , Chitosan/metabolism , Drug Carriers/metabolism , Drug Liberation , Endopeptidases/chemistry , Humans , Nanoparticles/metabolism , Streptococcus pneumoniae/drug effects
15.
Biochem Soc Trans ; 49(5): 2411-2429, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1397910

ABSTRACT

The importance of vaccine-induced protection was repeatedly demonstrated over the last three decades and emphasized during the recent COVID-19 pandemic as the safest and most effective way of preventing infectious diseases. Vaccines have controlled, and in some cases, eradicated global viral and bacterial infections with high efficiency and at a relatively low cost. Carbohydrates form the capsular sugar coat that surrounds the outer surface of human pathogenic bacteria. Specific surface-exposed bacterial carbohydrates serve as potent vaccine targets that broadened our toolbox against bacterial infections. Since first approved for commercial use, antibacterial carbohydrate-based vaccines mostly rely on inherently complex and heterogenous naturally derived polysaccharides, challenging to obtain in a pure, safe, and cost-effective manner. The introduction of synthetic fragments identical with bacterial capsular polysaccharides provided well-defined and homogenous structures that resolved many challenges of purified polysaccharides. The success of semisynthetic glycoconjugate vaccines against bacterial infections, now in different phases of clinical trials, opened up new possibilities and encouraged further development towards fully synthetic antibacterial vaccine solutions. In this mini-review, we describe the recent achievements in semi- and fully synthetic carbohydrate vaccines against a range of human pathogenic bacteria, focusing on preclinical and clinical studies.


Subject(s)
Anti-Bacterial Agents/immunology , Bacteria/immunology , Bacterial Infections/immunology , Carbohydrates/immunology , Glycoconjugates/immunology , Vaccines, Synthetic/immunology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/therapeutic use , Bacteria/drug effects , Bacterial Infections/microbiology , Bacterial Infections/prevention & control , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Carbohydrate Sequence , Carbohydrates/chemistry , Glycoconjugates/chemistry , Glycoconjugates/therapeutic use , Humans , Vaccines, Synthetic/chemistry , Vaccines, Synthetic/therapeutic use
16.
PLoS One ; 16(9): e0251951, 2021.
Article in English | MEDLINE | ID: covidwho-1394538

ABSTRACT

The purpose of this study was to explore potential mechanisms of cytotoxicity towards HeLa and HT29 cells displayed by Pediocin PA-1. We did this by carrying out sequence alignments and 3D modelling of related bacteriocins which have been studied in greater detail: Microcin E492, Enterocin AB heterodimer and Divercin V41. Microcin E492 interacts with Toll-Like Receptor 4 in order to activate an apoptosis reaction, sequence alignment showed a high homology between Pediocin PA-1 and Microcin E492 whereas 3D modelling showed Pediocin PA-1 interacting with TLR-4 in a way reminiscent of Microcin E492. Furthermore, Pediocin PA-1 had the highest homology with the Enterocin heterodimer, particularly chain A; Enterocin has also shown to cause an apoptotic response in cancer cells. Based on this we are led to strongly believe Pediocin PA-1 interacts with TLRs in order to cause cell death. If this is the case, it would explain the difference in cytotoxicity towards HeLa over HT29 cells, due to difference in expression of particular TLRs. Overall, we believe Pediocin PA-1 exhibits a dual effect which is dose dependant, like that of Microcin. Unfortunately, due to the COVID-19 pandemic, we were unable to carry out experiments in the lab, and the unavailability of important data meant we were unable to provide and validate out solid conclusions, but rather suggestions. However, bioinformatic analysis is still able to provide information regarding structure and sequence analysis to draw plausible and evidence based conclusions. We have been able to highlight interesting findings and how these could be translated into future research and therapeutics in order to improve the quality of treatment and life of cancer patients.


Subject(s)
Bacteriocins/chemistry , Bacteriocins/pharmacology , Pediocins/chemistry , Pediocins/pharmacology , Protein Conformation , Amino Acid Sequence , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Apoptosis/drug effects , Bacteriocins/genetics , Bridged-Ring Compounds/chemistry , Bridged-Ring Compounds/pharmacology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/virology , Cell Survival/drug effects , HT29 Cells , HeLa Cells , Humans , Models, Molecular , Pandemics , Pediocins/genetics , SARS-CoV-2/physiology , Sequence Homology, Amino Acid , Toll-Like Receptor 4/metabolism
17.
Mar Drugs ; 18(10)2020 Sep 26.
Article in English | MEDLINE | ID: covidwho-1389432

ABSTRACT

For a long time, algal chemistry from terrestrial to marine or freshwater bodies, especially chlorophytes, has fascinated numerous investigators to develop new drugs in the nutraceutical and pharmaceutical industries. As such, chlorophytes comprise a diverse structural class of secondary metabolites, having functional groups that are specific to a particular source. All bioactive compounds of chlorophyte are of great interest due to their supplemental/nutritional/pharmacological activities. In this review, a detailed description of the chemical diversity of compounds encompassing alkaloids, terpenes, steroids, fatty acids and glycerides, their subclasses and their structures are discussed. These promising natural products have efficiency in developing new drugs necessary in the treatment of various deadly pathologies (cancer, HIV, SARS-CoV-2, several inflammations, etc.). Marine chlorophyte, therefore, is portrayed as a pivotal treasure in the case of drugs having marine provenience. It is a domain of research expected to probe novel pharmaceutically or nutraceutically important secondary metabolites resulting from marine Chlorophyta. In this regard, our review aims to compile the isolated secondary metabolites having diverse chemical structures from chlorophytes (like Caulerpa ssp., Ulva ssp., Tydemania ssp., Penicillus ssp., Codium ssp., Capsosiphon ssp., Avrainvillea ssp.), their biological properties, applications and possible mode of action.


Subject(s)
Biological Products/pharmacology , Chlorophyta/chemistry , Chlorophyta/metabolism , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Biological Products/chemistry , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Humans , Neoplasms/drug therapy , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , SARS-CoV-2
18.
Molecules ; 26(6)2021 Mar 23.
Article in English | MEDLINE | ID: covidwho-1389468

ABSTRACT

Natural products are gaining more interest recently, much of which focuses on those derived from medicinal plants. The common chicory (Cichorium intybus L.), of the Astraceae family, is a prime example of this trend. It has been proven to be a feasible source of biologically relevant elements (K, Fe, Ca), vitamins (A, B1, B2, C) as well as bioactive compounds (inulin, sesquiterpene lactones, coumarin derivatives, cichoric acid, phenolic acids), which exert potent pro-health effects on the human organism. It displays choleretic and digestion-promoting, as well as appetite-increasing, anti-inflammatory and antibacterial action, all owing to its varied phytochemical composition. Hence, chicory is used most often to treat gastrointestinal disorders. Chicory was among the plants with potential against SARS-CoV-2, too. To this and other ends, roots, herb, flowers and leaves are used. Apart from its phytochemical applications, chicory is also used in gastronomy as a coffee substitute, food or drink additive. The aim of this paper is to present, in the light of the recent literature, the chemical composition and properties of chicory.


Subject(s)
Chicory/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Antiparasitic Agents/chemistry , Antiparasitic Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , COVID-19/drug therapy , Chicory/physiology , Cooking , Food Hypersensitivity/etiology , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Plants, Medicinal/chemistry
19.
Appl Biochem Biotechnol ; 194(2): 671-693, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1375835

ABSTRACT

The growth of respiratory diseases, as witnessed through the SARS and COVID-19 outbreaks, and antimicrobial-resistance together pose a serious threat to humanity. One reason for antimicrobial resistance is formation of bacterial biofilms. In this study the sulphated polysaccharides from green algae Chlamydomonas reinhardtii (Cr-SPs) is tested for its antibacterial and antibiofilm potential against Klebsiella pneumoniae and Serratia marcescens. Agar cup assay clearly indicated the antibacterial potential of Cr-SPs. Minimum inhibitory concentration (MIC50) of Cr-SPs against Klebsiella pneumoniae was found to be 850 µg/ml, and it is 800 µg/ml in Serratia marcescens. Time-kill and colony-forming ability assays suggest the concentration-dependent bactericidal potential of Cr-SPs. Cr-SPs showed 74-100% decrease in biofilm formation in a concentration-dependent manner by modifying the cell surface hydrophobic properties of these bacteria. Cr-SPs have also distorted preformed-biofilms by their ability to interact and destroy the extra polymeric substance and eDNA of the matured biofilm. Scanning electron microscopy analysis showed that Cr-SPs effectively altered the morphology of these bacterial cells and distorted the bacterial biofilms. Furthermore reduced protease, urease and prodigiosin pigment production suggest that Cr-SPs interferes the quorum sensing mechanism in these bacteria. The current study paves way towards developing Cr-SPs as a control strategy for treatment of respiratory tract infections.


Subject(s)
Biofilms/drug effects , Polysaccharides/pharmacology , Quorum Sensing/drug effects , Respiratory Tract Infections/drug therapy , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Biofilms/growth & development , COVID-19/drug therapy , COVID-19/virology , Chlorophyta/chemistry , Humans , Klebsiella pneumoniae/growth & development , Klebsiella pneumoniae/pathogenicity , Microbial Sensitivity Tests , Polysaccharides/chemistry , Respiratory Tract Infections/microbiology , SARS-CoV-2/drug effects , Serratia marcescens/growth & development , Serratia marcescens/pathogenicity
20.
J Nat Prod ; 83(12): 3493-3501, 2020 12 24.
Article in English | MEDLINE | ID: covidwho-1351918

ABSTRACT

Svalbardines A and B (1 and 2) and annularin K (3) were isolated from cultures of Poaceicola sp. E1PB, an endophyte isolated from the petals of Papaver dahlianum from Svalbard, Norway. Svalbardine A (1) is a pyrano[3,2-c]chromen-4-one, a new analogue of citromycetin. Svalbardine B (2) displays an unprecedented carbon skeleton based on a 5'-benzyl-spiro[chroman-3,7'-isochromene]-4,8'-dione core. Annularin K (3) is a hydroxylated derivative of annularin D. The structure of these new polyketides, along with those of known compounds 4-6, was established by spectrometric analysis, including extensive ESI-CID-MSn processing in the case of svalbardine B (2).


Subject(s)
Ascomycota/chemistry , Spectrometry, Mass, Electrospray Ionization/methods , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Arctic Regions , Microbial Sensitivity Tests , Molecular Structure , Spectrum Analysis
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