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1.
Int J Mol Sci ; 23(4)2022 Feb 13.
Article in English | MEDLINE | ID: covidwho-1686819

ABSTRACT

The COVID-19 pandemic has evidenced the urgent need for the discovery of broad-spectrum antiviral therapies that could be deployed in the case of future emergence of novel viral threats, as well as to back up current therapeutic options in the case of drug resistance development. Most current antivirals are directed to inhibit specific viruses since these therapeutic molecules are designed to act on a specific viral target with the objective of interfering with a precise step in the replication cycle. Therefore, antimicrobial peptides (AMPs) have been identified as promising antiviral agents that could help to overcome this limitation and provide compounds able to act on more than a single viral family. We evaluated the antiviral activity of an amphibian peptide known for its strong antimicrobial activity against both Gram-positive and Gram-negative bacteria, namely Temporin L (TL). Previous studies have revealed that TL is endowed with widespread antimicrobial activity and possesses marked haemolytic activity. Therefore, we analyzed TL and a previously identified TL derivative (Pro3, DLeu9 TL, where glutamine at position 3 is replaced with proline, and the D-Leucine enantiomer is present at position 9) as well as its analogs, for their activity against a wide panel of viruses comprising enveloped, naked, DNA and RNA viruses. We report significant inhibition activity against herpesviruses, paramyxoviruses, influenza virus and coronaviruses, including SARS-CoV-2. Moreover, we further modified our best candidate by lipidation and demonstrated a highly reduced cytotoxicity with improved antiviral effect. Our results show a potent and selective antiviral activity of TL peptides, indicating that the novel lipidated temporin-based antiviral agents could prove to be useful additions to current drugs in combatting rising drug resistance and epidemic/pandemic emergencies.


Subject(s)
Amphibian Proteins/pharmacology , Amphibians/metabolism , Antimicrobial Cationic Peptides/pharmacology , Antiviral Agents/chemistry , DNA Viruses/drug effects , RNA Viruses/drug effects , Amino Acid Sequence , Amphibian Proteins/chemistry , Amphibian Proteins/metabolism , Animals , Antimicrobial Cationic Peptides/chemistry , Antimicrobial Cationic Peptides/metabolism , Antiviral Agents/pharmacology , Cell Survival/drug effects , Chlorocebus aethiops , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Lipids/chemistry , SARS-CoV-2/drug effects , Vero Cells
2.
Chem Biodivers ; 18(11): e2100674, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1615945

ABSTRACT

Chemical investigation on a Streptomyces sp. strain MS180069 isolated from a sediment sample collected from the South China Sea, yielded the new benzo[f]isoindole-dione alkaloid, bhimamycin J (1). The structure was determined by extensive spectroscopic analysis, including HRMS, 1D, 2D NMR, and X-ray diffraction techniques. A molecular docking study revealed 1 as a new molecular motif that binds with human angiotensin converting enzyme2 (ACE2), recently described as the cell surface receptor responsible for uptake of 2019-CoV-2. Using enzyme assays we confirm that 1 inhibits human ACE2 79.7 % at 25 µg/mL.


Subject(s)
Alkaloids/chemistry , Geologic Sediments/microbiology , Isoindoles/chemistry , Streptomyces/chemistry , Alkaloids/metabolism , Alkaloids/pharmacology , Alkaloids/therapeutic use , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/metabolism , Binding Sites , COVID-19/drug therapy , COVID-19/virology , Fungi/drug effects , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Isoindoles/isolation & purification , Isoindoles/metabolism , Isoindoles/pharmacology , Magnetic Resonance Spectroscopy , Molecular Conformation , Molecular Docking Simulation , SARS-CoV-2/isolation & purification , Streptomyces/isolation & purification , Streptomyces/metabolism
3.
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
4.
Sci Rep ; 11(1): 22543, 2021 11 19.
Article in English | MEDLINE | ID: covidwho-1526103

ABSTRACT

Microbial contamination is one of the major dreadful problems that raises hospitalization, morbidity and mortality rates globally, which subsequently obstructs socio-economic progress. The continuous misuse and overutilization of antibiotics participate mainly in the emergence of microbial resistance. To circumvent such a multidrug-resistance phenomenon, well-defined nanocomposite structures have recently been employed. In the current study, a facile, novel and cost-effective approach was applied to synthesize Ag@Ag2O core-shell nanocomposites (NCs) via chemical method. Several techniques were used to determine the structural, morphological, and optical characteristics of the as-prepared NCs. XRD, Raman, FTIR, XPS and SAED analysis revealed a crystalline hybrid structure of Ag core and Ag2O shell. Besides, SEM and HRTEM micrographs depicted spherical nanoparticles with size range of 19-60 nm. Additionally, zeta potential and fluorescence spectra illustrated aggregated nature of Ag@Ag2O NCs by - 5.34 mV with fluorescence emission peak at 498 nm. Ag@Ag2O NCs exhibited higher antimicrobial, antibiofilm, and algicidal activity in dose-dependent behavior. Interestingly, a remarkable mycocidal potency by 50 µg of Ag@Ag2O NCs against Candida albican; implying promising activity against COVID-19 white fungal post-infections. Through assessing cytotoxicity, Ag@Ag2O NCs exhibited higher safety against Vero cells than bulk silver nitrate by more than 100-fold.


Subject(s)
Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Biofilms/drug effects , Nanocomposites/chemistry , Oxides/chemistry , Silver Compounds/chemistry , Animals , Anti-Infective Agents/chemical synthesis , Candida albicans/drug effects , Cell Survival/drug effects , Chlorella vulgaris/drug effects , Chlorocebus aethiops , Disinfectants/chemical synthesis , Disinfectants/chemistry , Disinfectants/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Metal Nanoparticles/chemistry , Oxides/chemical synthesis , Pseudomonas aeruginosa/drug effects , Silver Compounds/chemical synthesis , Silver Nitrate/pharmacology , Staphylococcus aureus/drug effects , Vero Cells
5.
Molecules ; 26(22)2021 Nov 20.
Article in English | MEDLINE | ID: covidwho-1524087

ABSTRACT

A series of methyl ß-D-galactopyranoside (MGP, 1) analogs were selectively acylated with cinnamoyl chloride in anhydrous N,N-dimethylformamide/triethylamine to yield 6-O-substitution products, which was subsequently converted into 2,3,4-tri-O-acyl analogs with different acyl halides. Analysis of the physicochemical, elemental, and spectroscopic data of these analogs revealed their chemical structures. In vitro antimicrobial testing against five bacteria and two fungi and the prediction of activity spectra for substances (PASS) showed promising antifungal functionality comparing to their antibacterial activities. Minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) tests were conducted for four compounds (4, 5, 6, and 9) based on their activity. MTT assay showed low antiproliferative activity of compound 9 against Ehrlich's ascites carcinoma (EAC) cells with an IC50 value of 2961.06 µg/mL. Density functional theory (DFT) was used to calculate the thermodynamic and physicochemical properties whereas molecular docking identified potential inhibitors of the SARS-CoV-2 main protease (6Y84). A 150-ns molecular dynamics simulation study revealed the stable conformation and binding patterns in a stimulating environment. In-silico ADMET study suggested all the designed molecules to be non-carcinogenic, with low aquatic and non-aquatic toxicity. In summary, all these antimicrobial, anticancer and in silico studies revealed that newly synthesized MGP analogs possess promising antiviral activity, to serve as a therapeutic target for COVID-19.


Subject(s)
Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Galactose/analogs & derivatives , Animals , Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/pharmacokinetics , Antifungal Agents/chemistry , Antifungal Agents/pharmacokinetics , Antifungal Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacokinetics , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Antiviral Agents/pharmacokinetics , Antiviral Agents/pharmacology , COVID-19/drug therapy , Cell Line, Tumor , Coronavirus 3C Proteases/chemistry , Galactose/chemistry , Galactose/pharmacokinetics , Galactose/pharmacology , Gram-Positive Bacteria/drug effects , Mice , Microbial Sensitivity Tests , Molecular Docking Simulation , Molecular Dynamics Simulation , SARS-CoV-2/enzymology , Static Electricity , Thermodynamics
6.
Int J Mol Sci ; 22(20)2021 Oct 12.
Article in English | MEDLINE | ID: covidwho-1480791

ABSTRACT

Novel xanthine and imidazolone derivatives were synthesized based on oxazolone derivatives 2a-c as a key intermediate. The corresponding xanthine 3-5 and imidazolone derivatives 6-13 were obtained via reaction of oxazolone derivative 2a-c with 5,6-diaminouracils 1a-e under various conditions. Xanthine compounds 3-5 were obtained by cyclocondensation of 5,6-diaminouracils 1a-c with different oxazolones in glacial acetic acid. Moreover, 5,6-diaminouracils 1a-e were reacted with oxazolones 2a-c in presence of drops of acetic acid under fused condition yielding the imidazolone derivatives 6-13. Furthermore, Schiff base of compounds 14-16 were obtained by condensing 5,6-diaminouracils 1a,b,e with 4-dimethylaminobenzaldehyde in acetic acid. The structural identity of the resulting compounds was resolved by IR, 1H-, 13C-NMR and Mass spectral analyses. The novel synthesized compounds were screened for their antifungal and antibacterial activities. Compounds 3, 6, 13 and 16 displayed the highest activity against Escherichia coli as revealed from the IC50 values (1.8-1.9 µg/mL). The compound 16 displayed a significant antifungal activity against Candia albicans (0.82 µg/mL), Aspergillus flavus (1.2 µg/mL) comparing to authentic antibiotics. From the TEM microgram, the compounds 3, 12, 13 and 16 exhibited a strong deformation to the cellular entities, by interfering with the cell membrane components, causing cytosol leakage, cellular shrinkage and irregularity to the cell shape. In addition, docking study for the most promising antimicrobial tested compounds depicted high binding affinity against acyl carrier protein domain from a fungal type I polyketide synthase (ACP), and Baumannii penicillin- binding protein (PBP). Moreover, compound 12 showed high drug- likeness, and excellent pharmacokinetics, which needs to be in focus for further antimicrobial drug development. The most promising antimicrobial compounds underwent theoretical investigation using DFT calculation.


Subject(s)
Anti-Infective Agents/chemical synthesis , Imidazoles/chemistry , Uracil/chemistry , Xanthines/chemistry , Animals , Anti-Infective Agents/metabolism , Anti-Infective Agents/pharmacology , Binding Sites , Candida albicans/drug effects , Cell Survival/drug effects , Chlorocebus aethiops , DNA Gyrase/chemistry , DNA Gyrase/metabolism , Density Functional Theory , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Half-Life , Imidazoles/metabolism , Imidazoles/pharmacology , Microbial Sensitivity Tests , Molecular Docking Simulation , Polyketide Synthases/chemistry , Polyketide Synthases/metabolism , Structure-Activity Relationship , Thermodynamics , Vero Cells
7.
BMC Pulm Med ; 20(1): 233, 2020 Aug 31.
Article in English | MEDLINE | ID: covidwho-1257932

ABSTRACT

BACKGROUND: Lower respiratory tract infection (LRIs) is very common both in terms of community-acquired infection and hospital-acquired infection. Sputum and bronchoalveolar lavage fluid (BALF) are the most important specimens obtained from patients with LRI. The choice of antibiotic with which to treat LRI usually depends on the antimicrobial sensitivity of bacteria isolated from sputum and BALF. However, differences in the antimicrobial sensitivity of pathogens isolated from sputum and BALF have not been evaluated. METHODS: A retrospective study was conducted to analyze the differences between sputum and BALF samples in terms of pathogen isolation and antimicrobial sensitivity in hospitalized patients with LRI. RESULTS: Between 2013 and 2015, quality evaluation of sputum samples was not conducted before performing sputum culture; however, between 2016 and 2018, quality evaluation of sputum samples was conducted first, and only quality-assured samples were cultured. The numbers of sputum and BALF in 2013-2015 were 15,549 and 1671, while those in 2016-2018 were 12,055 and 3735, respectively. The results of pathogen culture showed that Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus, Hemophilus influenzae, Escherichia coli, Stenotrophomonas maltophilia, and Streptococcus pneumoniae were in the top ten pathogens isolated from sputum and BALF. An antimicrobial susceptibility test showed that the susceptibility of BALF isolates to most antibiotics was higher compared with the susceptibility of sputum isolates, especially after quality control of sputum samples (2016-2018). CONCLUSIONS: Our findings suggest that caution is needed in making therapeutic choices for patients with LRI when using antimicrobial sensitivity results from sputum isolates as opposed to BALF isolates.


Subject(s)
Bacterial Infections/microbiology , Bronchoalveolar Lavage Fluid/microbiology , Microbial Sensitivity Tests , Respiratory System/microbiology , Sputum/microbiology , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/epidemiology , China/epidemiology , Escherichia coli/drug effects , Escherichia coli/isolation & purification , Female , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/isolation & purification , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/isolation & purification , Hospitals, Teaching , Humans , Male , Retrospective Studies , Staphylococcus aureus/isolation & purification
8.
Sci Rep ; 11(1): 12410, 2021 06 14.
Article in English | MEDLINE | ID: covidwho-1268005

ABSTRACT

In situ generation of antibacterial and antiviral agents by harnessing the catalytic activity of enzymes on surfaces provides an effective eco-friendly approach for disinfection. The perhydrolase (AcT) from Mycobacterium smegmatis catalyzes the perhydrolysis of acetate esters to generate the potent disinfectant, peracetic acid (PAA). In the presence of AcT and its two substrates, propylene glycol diacetate and H2O2, sufficient and continuous PAA is generated over an extended time to kill a wide range of bacteria with the enzyme dissolved in aqueous buffer. For extended self-disinfection, however, active and stable AcT bound onto or incorporated into a surface coating is necessary. In the current study, an active, stable and reusable AcT-based coating was developed by incorporating AcT into a polydopamine (PDA) matrix in a single step, thereby forming a biocatalytic composite onto a variety of surfaces. The resulting AcT-PDA composite coatings on glass, metal and epoxy surfaces yielded up to 7-log reduction of Gram-positive and Gram-negative bacteria when in contact with the biocatalytic coating. This composite coating also possessed potent antiviral activity, and dramatically reduced the infectivity of a SARS-CoV-2 pseudovirus within minutes. The single-step approach enables rapid and facile fabrication of enzyme-based disinfectant composite coatings with high activity and stability, which enables reuse following surface washing. As a result, this enzyme-polymer composite technique may serve as a general strategy for preparing antibacterial and antiviral surfaces for applications in health care and common infrastructure safety, such as in schools, the workplace, transportation, etc.


Subject(s)
Anti-Bacterial Agents/chemistry , Antiviral Agents/chemistry , Bacterial Proteins/chemistry , Hydrolases/chemistry , Indoles/chemistry , Polymers/chemistry , Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/pharmacology , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , COVID-19/pathology , COVID-19/virology , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/metabolism , Coated Materials, Biocompatible/pharmacology , Drug Stability , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Hydrolases/genetics , Hydrolases/metabolism , Kinetics , Mycobacterium smegmatis/enzymology , Peracetic Acid/metabolism , Recombinant Proteins/biosynthesis , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification , SARS-CoV-2/drug effects
9.
Biomolecules ; 11(5)2021 05 17.
Article in English | MEDLINE | ID: covidwho-1234665

ABSTRACT

Cm-p5 is a snail-derived antimicrobial peptide, which demonstrated antifungal activity against the pathogenic strains of Candida albicans. Previously we synthetized a cyclic monomer as well as a parallel and an antiparallel dimer of Cm-p5 with improved antifungal activity. Considering the alarming increase of microbial resistance to conventional antibiotics, here we evaluated the antimicrobial activity of these derivatives against multiresistant and problematic bacteria and against important viral agents. The three peptides showed a moderate activity against Pseudomonas aeruginosa, Klebsiella pneumoniae Extended Spectrum ß-Lactamase (ESBL), and Streptococcus agalactiae, with MIC values > 100 µg/mL. They exerted a considerable activity with MIC values between 25-50 µg/mL against Acinetobacter baumanii and Enterococcus faecium. In addition, the two dimers showed a moderate activity against Pseudomonas aeruginosa PA14. The three Cm-p5 derivatives inhibited a virulent extracellular strain of Mycobacterium tuberculosis, in a dose-dependent manner. Moreover, they inhibited Herpes Simplex Virus 2 (HSV-2) infection in a concentration-dependent manner, but had no effect on infection by the Zika Virus (ZIKV) or pseudoparticles of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2). At concentrations of >100 µg/mL, the three new Cm-p5 derivatives showed toxicity on different eukaryotic cells tested. Considering a certain cell toxicity but a potential interesting activity against the multiresistant strains of bacteria and HSV-2, our compounds require future structural optimization.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antimicrobial Cationic Peptides/chemistry , Antiviral Agents/pharmacology , Drug Resistance, Multiple, Bacterial/drug effects , Herpesvirus 2, Human/drug effects , Amino Acid Sequence , Animals , Anti-Bacterial Agents/chemistry , Antimicrobial Cationic Peptides/pharmacology , Antiviral Agents/chemistry , Candida albicans/drug effects , Cell Line , Cell Survival/drug effects , Dimerization , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Microbial Sensitivity Tests , SARS-CoV-2/drug effects
10.
Z Naturforsch C J Biosci ; 76(11-12): 467-480, 2021 Nov 25.
Article in English | MEDLINE | ID: covidwho-1202282

ABSTRACT

A series of ethyl 2-(2-(arylidene)hydrazinyl)thiazole-4-carboxylates (2a-r) was synthesized in two steps from thiosemicarbazones (1a-r), which were cyclized with ethyl bromopyruvate to ethyl 2-(2-(arylidene)hydrazinyl)thiazole-4-carboxylates (2a-r). The structures of compounds (2a-r) were established by FT-IR, 1H- and 13C-NMR. The structure of compound 2a was confirmed by HRMS. The compounds (2a-r) were then evaluated for their antimicrobial and antioxidant assays. The antioxidant studies revealed, ethyl 2-(2-(4-hydroxy-3-methoxybenzylidene)hydrazinyl)thiazole-4-carboxylate (2g) and ethyl 2-(2-(1-phenylethylidene)hydrazinyl)thiazole-4-carboxylate (2h) as promising antioxidant agents with %FRSA: 84.46 ± 0.13 and 74.50 ± 0.37, TAC: 269.08 ± 0.92 and 269.11 ± 0.61 and TRP: 272.34 ± 0.87 and 231.11 ± 0.67 µg AAE/mg dry weight of compound. Beside bioactivities, density functional theory (DFT) methods were used to study the electronic structure and properties of synthesized compounds (2a-m). The potential of synthesized compounds for possible antiviral targets is also predicted through molecular docking methods. The compounds 2e and 2h showed good binding affinities and inhibition constants to be considered as therapeutic target for Mpro protein of SARS-CoV-2 (COVID-19). The present in-depth analysis of synthesized compounds will put them under the spot light for practical applications as antioxidants and the modification in structural motif may open the way for COVID-19 drug.


Subject(s)
Anti-Infective Agents/chemical synthesis , Antioxidants/chemistry , Antiviral Agents/chemistry , Molecular Docking Simulation , Thiazoles/chemistry , Viral Matrix Proteins/chemistry , Anti-Infective Agents/metabolism , Anti-Infective Agents/pharmacology , Antiviral Agents/chemical synthesis , Antiviral Agents/metabolism , Binding Sites , COVID-19/pathology , COVID-19/virology , Density Functional Theory , Fusarium/drug effects , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , SARS-CoV-2/enzymology , SARS-CoV-2/isolation & purification , Structure-Activity Relationship , Thiazoles/metabolism , Viral Matrix Proteins/metabolism
11.
Bioorg Chem ; 112: 104925, 2021 07.
Article in English | MEDLINE | ID: covidwho-1198631

ABSTRACT

Antibiotic resistance and emerging viral pandemics have posed an urgent need for new anti-infective drugs. By screening our microbial extract library against the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the notorious ESKAPE pathogens, an active fraction was identified and purified, leading to an initial isolation of adipostatins A (1) and B (2). In order to diversify the chemical structures of adipostatins toward enhanced biological activities, a type III polyketide synthase was identified from the native producer, Streptomyces davawensis DSM101723, and was subsequently expressed in an E. coli host, resulting in the isolation of nine additional adipostatins 3-11, including two new analogs (9 and 11). The structures of 1-11 were established by HRMS, NMR, and chemical derivatization, including using a microgram-scale meta-chloroperoxybenzoic acid epoxidation-MS/MS analysis to unambiguously determine the double bond position in the alkyl chain. The present study discovered SARS-CoV-2 main protease inhibitory activity for the class of adipostatins for the first time. Several of the adipostatins isolated also exhibited antimicrobial activity against selected ESKAPE pathogens.


Subject(s)
Acyltransferases/metabolism , Anti-Infective Agents/chemistry , Bacterial Proteins/metabolism , Resorcinols/chemistry , Acyltransferases/antagonists & inhibitors , Acyltransferases/classification , Acyltransferases/genetics , Anti-Infective Agents/isolation & purification , Anti-Infective Agents/metabolism , Anti-Infective Agents/pharmacology , Bacterial Proteins/antagonists & inhibitors , Bacterial Proteins/classification , Bacterial Proteins/genetics , COVID-19/pathology , COVID-19/virology , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/metabolism , Drug Evaluation, Preclinical , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Molecular Conformation , Phylogeny , Recombinant Proteins/biosynthesis , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification , Resorcinols/isolation & purification , Resorcinols/metabolism , Resorcinols/pharmacology , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Streptomyces/enzymology , Tandem Mass Spectrometry
12.
Int J Biol Macromol ; 181: 990-1002, 2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1188608

ABSTRACT

Coronaviruses (CoV) are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). We succeeded in preparing disinfectant cellulose-based wipes treated with antimicrobial and antiviral silver nanoparticles to be used for prevention of contamination and transmission of several pathogenic viruses and microbes to human in critical areas such as hospitals and healthcare centers especially coronavirus. In this work, the antimicrobial and antiviral activities of silver nanoparticles (AgNPs) prepared with four different techniques were investigated for the utilization as a disinfectant for cellulose-based wipes. These four methods are namely; 1) trisodium citrate with cotton yarn as a reducing agent, 2) preparing AgNP's using aqueous solution of PVA in the presence of glucose, 3) trisodium citrate with cotton fabric as a reducing agent, and 4) photochemical reaction of polyacrylic acid and silver nitrate solution. Polyester/viscose blended spunlace nonwoven fabrics as cellulose based fabrics were treated with the prepared silver nanoparticles to be used as surfaces disinfection wipes. The properties of the nonwoven fabrics were examined including thickness, tensile strength in dry and wet conditions in both machine direction (MD) and cross-machine direction (CMD), bursting strength, air permeability, water permeability and surface wettability. Characterization of the AgNPs was carried out in terms of UV-VIS spectroscopy, TEM, SEM, and Zeta potential analysis. The assessment of AgNPs active solutions for antimicrobial and antiviral activities was evaluated. The results obtained from the analyses of the AgNPs samples prepared with different techniques showed good uniformity and stability of the particles, as well uniform coating of the AgNPs on the fibers. Additionally, there is a significant effect of the AgNPs preparation method on their disinfectant performance that proved its effectiveness against coronavirus (MERS-CoV), S. aureus and B. subtilis as Gram-positive bacteria, E. coli and P. mirabilis as Gram-negative bacteria, A. niger and C. albicans fungi.


Subject(s)
COVID-19/prevention & control , Cellulose/chemistry , Coronavirus/drug effects , Disinfectants/chemistry , Metal Nanoparticles/chemistry , SARS-CoV-2/drug effects , Silver/chemistry , Acrylic Resins/chemistry , Anti-Bacterial Agents/chemistry , Anti-Infective Agents/chemistry , Antiviral Agents/chemistry , Citrates/chemistry , Cotton Fiber , Fungi/drug effects , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Green Chemistry Technology , Microbial Sensitivity Tests , Silver Nitrate/chemistry
13.
ACS Appl Mater Interfaces ; 13(4): 5678-5690, 2021 Feb 03.
Article in English | MEDLINE | ID: covidwho-1065790

ABSTRACT

The COVID-19 pandemic has clearly shown the importance of developments in fabrication of advanced protective equipment. This study investigates the potential of using multifunctional electrospun poly(methyl methacrylate) (PMMA) nanofibers decorated with ZnO nanorods and Ag nanoparticles (PMMA/ZnO-Ag NFs) in protective mats. Herein, the PMMA/ZnO-Ag NFs with an average diameter of 450 nm were simply prepared on a nonwoven fabric by directly electrospinning from solutions containing PMMA, ZnO nanorods, and Ag nanoparticles. The novel material showed high performance with four functionalities (i) antibacterial agent for killing of Gram-negative and Gram-positive bacteria, (ii) antiviral agent for inhibition of corona and influenza viruses, (iii) photocatalyst for degradation of organic pollutants, enabling a self-cleaning protective mat, and (iv) reusable surface-enhanced Raman scattering substrate for quantitative analysis of trace pollutants on the nanofiber. This multi-functional material has high potential for use in protective clothing applications by providing passive and active protection pathways together with sensing capabilities.


Subject(s)
Anti-Infective Agents/chemistry , Metal Nanoparticles/chemistry , Silver/chemistry , Zinc Oxide/chemistry , Anti-Bacterial Agents/chemistry , Antiviral Agents/chemistry , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Microbial Sensitivity Tests , Nanofibers/chemistry , Nanotubes/chemistry , Polymethyl Methacrylate/chemistry , Spectrum Analysis, Raman
14.
Bioorg Chem ; 105: 104354, 2020 12.
Article in English | MEDLINE | ID: covidwho-838154

ABSTRACT

Three series of nanosized-formazan analogues were synthesized from the reaction of dithiazone with various types of α-haloketones (ester and acetyl substituted hydrazonoyl chlorides and phenacyl bromides) in sodium ethoxide solution. The structure and the crystal size of the new synthesized derivatives were assured based on the spectral analyses, XRD and SEM data. The antibacterial and antifungal activities were evaluated by agar diffusion technique. The results showed mild to moderate antibacterial activities and moderate to potent antifungal activities. Significant antifungal activities were observed for four derivatives 3a, 3d, 5a and 5g on the pathogenic fungal strains; Aspergillus flavus and Candida albicans with inhibition zone ranging from 16 to 20 mm. Molecular docking simulations of the synthesized compounds into leucyl-tRNA synthetase editing domain of Candida albicans suggested that most formazan analogues can fit deeply forming stable complexes in the active site. Furthermore, we utilized the docking approach to examine the potential of these compounds to inhibit SARS-CoV-2 3CLpro. The results were very promising verifying these formazan analogues as a hopeful antiviral agents.


Subject(s)
Anti-Infective Agents/chemical synthesis , Coronavirus 3C Proteases/metabolism , Formazans/chemistry , Molecular Docking Simulation , Nanostructures/chemistry , SARS-CoV-2/metabolism , Anti-Infective Agents/metabolism , Anti-Infective Agents/pharmacology , Aspergillus flavus/drug effects , Binding Sites , COVID-19/pathology , COVID-19/virology , Candida albicans/drug effects , Catalytic Domain , Coronavirus 3C Proteases/chemistry , Formazans/metabolism , Formazans/pharmacology , Fungal Proteins/chemistry , Fungal Proteins/metabolism , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Leucine-tRNA Ligase/chemistry , Leucine-tRNA Ligase/metabolism , SARS-CoV-2/isolation & purification
15.
Sci Rep ; 10(1): 13875, 2020 08 17.
Article in English | MEDLINE | ID: covidwho-720847

ABSTRACT

Respiratory protection is key in infection prevention of airborne diseases, as highlighted by the COVID-19 pandemic for instance. Conventional technologies have several drawbacks (i.e., cross-infection risk, filtration efficiency improvements limited by difficulty in breathing, and no safe reusability), which have yet to be addressed in a single device. Here, we report the development of a filter overcoming the major technical challenges of respiratory protective devices. Large-pore membranes, offering high breathability but low bacteria capture, were functionalized to have a uniform salt layer on the fibers. The salt-functionalized membranes achieved high filtration efficiency as opposed to the bare membrane, with differences of up to 48%, while maintaining high breathability (> 60% increase compared to commercial surgical masks even for the thickest salt filters tested). The salt-functionalized filters quickly killed Gram-positive and Gram-negative bacteria aerosols in vitro, with CFU reductions observed as early as within 5 min, and in vivo by causing structural damage due to salt recrystallization. The salt coatings retained the pathogen inactivation capability at harsh environmental conditions (37 °C and a relative humidity of 70%, 80% and 90%). Combination of these properties in one filter will lead to the production of an effective device, comprehensibly mitigating infection transmission globally.


Subject(s)
Air Filters/microbiology , Anti-Bacterial Agents/chemistry , Betacoronavirus , Coronavirus Infections/prevention & control , Masks/microbiology , Membranes, Artificial , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Respiratory Protective Devices/microbiology , Sodium Chloride/chemistry , Aerosols , Anti-Bacterial Agents/pharmacology , COVID-19 , Coronavirus Infections/transmission , Coronavirus Infections/virology , Crystallization , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Hot Temperature , Humans , Humidity , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , SARS-CoV-2 , Sodium Chloride/pharmacology
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