Interference of Polydatin/Resveratrol in the ACE2:Spike Recognition during COVID-19 Infection. A Focus on Their Potential Mechanism of Action through Computational and Biochemical Assays

In the search for new therapeutic strategies to contrast SARS-CoV-2, we here studied the interaction of polydatin (PD) and resveratrol (RESV)—two natural stilbene polyphenols with manifold, well known biological activities—with Spike, the viral protein essential for virus entry into host cells, and ACE2, the angiotensin-converting enzyme present on the surface of multiple cell types (including respiratory epithelial cells) which is the main host receptor for Spike binding. Molecular Docking simulations evidenced that both compounds can bind Spike, ACE2 and the ACE2:Spike complex with good affinity, although the interaction of PD appears stronger than that of RESV on all the investigated targets. Preliminary biochemical assays revealed a significant inhibitory activity of the ACE2:Spike recognition with a dose-response effect only in the case of PD.

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Effect of calcium on the interaction of Acinetobacter baumannii with human respiratory epithelial cells

BMC Microbiology ◽

10.1186/s12866-019-1643-z ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Yi Chen ◽

Tingjun Shao ◽

Sanhua Fang ◽

Ping Pan ◽

Jiahui Jiang ◽

...

Keyword(s):

Epithelial Cells ◽

Acinetobacter Baumannii ◽

Host Cells ◽

Effective Control ◽

Respiratory Epithelial Cells ◽

Cellular Analysis ◽

Bacterial Interaction ◽

Dependent Cell ◽

Human Respiratory Epithelial Cells ◽

Respiratory Epithelial

Abstract Background Investigating the factors that influence Acinetobacter baumannii(Ab) adhesion/invasion of host cells is important to understand its pathogenicity. Metal cations have been shown to play an important role in regulating the biofilm formation and increasing the virulence of Ab; however, the effect of calcium on host-bacterial interaction has yet to be clarified. Here, the dynamic process of the interaction between Ab and human respiratory epithelial cells and the effect of calcium on host-bacterial interaction were explored using microscopic imaging, quantitative PCR and real time cellular analysis (RTCA). Results The concentration of calcium, multiplicity of infection and co-culture time were all demonstrated to have effects on host-bacterial interaction. A unique “double peak” phenomenon changed to a sharp “single peak” phenomenon during the process of Ab infection under the effect of calcium was observed in the time-dependent cell response profiles. Moreover, calcium can increase Ab adhesion/invasion of epithelial cells by regulating the expression of Ab-related genes (ompA, bfmRS, abaI). Conclusions Effective control of calcium concentrations can provide new approaches for the prevention and treatment of multi-drug resistant Ab.

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Role of Pht Proteins in Attachment of Streptococcus pneumoniae to Respiratory Epithelial Cells

Infection and Immunity ◽

10.1128/iai.00699-13 ◽

2014 ◽

Vol 82 (4) ◽

pp. 1683-1691 ◽

Cited By ~ 30

Author(s):

Anna Kallio ◽

Kirsi Sepponen ◽

Philippe Hermand ◽

Philippe Denoël ◽

Fabrice Godfroid ◽

...

Keyword(s):

Epithelial Cells ◽

Bacterial Attachment ◽

Surface Proteins ◽

Lung Epithelial Cells ◽

Host Cells ◽

Respiratory Epithelial Cells ◽

Relative Significance ◽

Mucosal Surfaces ◽

Respiratory Epithelial

ABSTRACTPneumococcal adherence to mucosal surfaces is a critical step in nasopharyngeal colonization, but so far few pneumococcal adhesins involved in the interaction with host cells have been identified. PhtA, PhtB, PhtD, and PhtE are conserved pneumococcal surface proteins that have proven promising as vaccine candidates. One suggested virulence function of Pht proteins is to mediate adherence at the respiratory mucosa. In this study, we assessed the role of Pht proteins in pneumococcal binding to respiratory epithelial cells. Pneumococci were incubated with human nasopharyngeal epithelial cells (Detroit-562) and lung epithelial cells (A549 and NCI-H292), and the proportion of bound bacteria was measured by plating viable counts. Strains R36A (unencapsulated), D39 (serotype 2), 43 (serotype 3), 4-CDC (serotype 4), and 2737 (serotype 19F) with one or more of the four homologous Pht proteins deleted were compared with their wild-type counterparts. Also, the effect of anti-PhtD antibodies on the adherence of strain 2737 to the respiratory epithelial cells was studied. Our results suggest that Pht proteins play a role in pneumococcal adhesion to the respiratory epithelium. We also found that antibody to PhtD is able to inhibit bacterial attachment to the cells, suggesting that antibodies against PhtD present at mucosal surfaces might protect from pneumococcal attachment and subsequent colonization. However, the relative significance of Pht proteins to the ability of pneumococci to bindin vitroto epithelial cells depends on the genetic background and the capsular serotype of the strain.

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Effect of Calcium on the Interaction of Acinetobacter baumannii with Human Respiratory Epithelial Cells

10.21203/rs.2.14268/v2 ◽

2019 ◽

Author(s):

Yi Chen ◽

Tingjun Shao ◽

Sanhua Fang ◽

Ping Pan ◽

Jiahui Jiang ◽

...

Keyword(s):

Epithelial Cells ◽

Acinetobacter Baumannii ◽

Host Cells ◽

Effective Control ◽

Respiratory Epithelial Cells ◽

Cellular Analysis ◽

Bacterial Interaction ◽

Dependent Cell ◽

Human Respiratory Epithelial Cells ◽

Respiratory Epithelial

Abstract Background: Investigating the factors that influence Acinetobacter baumannii (Ab) adhesion/invasion of host cells is important to understand its pathogenicity. Metal cations have been shown to play an important role in regulating the biofilm formation and increasing the virulence of Ab; however, the effect of calcium on host-bacterial interaction has yet to be clarified. Here, the dynamic process of the interaction between Ab and human respiratory epithelial cells and the effect of calcium on host-bacterial interaction were explored using the technologies of microscopic imaging, quantitative PCR and real time cellular analysis (RTCA). Results: The concentration of calcium, multiplicity of infection and co-culture time were demonstrated to have effects on host-bacterial interaction. A unique "double peak" phenomenon changed to a sharp "single peak" phenomenon during the process of Ab infection under the effect of calcium were determined based on the time-dependent cell response profiles. Moreover, calcium can increase Ab adhesion/invasion of epithelial cells by regulating the expression of Ab-related genes ( ompA , bfmRS , abaI ). Conclusions: Effective control of calcium concentrations can provide new ideas for the prevention and treatment of multi-drug resistant Ab.

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Effects of Calcium on the Interactions of Acinetobacter baumannii with Human Respiratory Epithelial Cells

10.21203/rs.2.14268/v1 ◽

2019 ◽

Author(s):

Yi Chen ◽

Tingjun Shao ◽

Sanhua Fang ◽

Ping Pan ◽

Jiahui Jiang ◽

...

Keyword(s):

Epithelial Cells ◽

Acinetobacter Baumannii ◽

Host Cells ◽

Effective Control ◽

Respiratory Epithelial Cells ◽

Bacterial Interactions ◽

Cellular Analysis ◽

Dependent Cell ◽

Human Respiratory Epithelial Cells ◽

Respiratory Epithelial

Abstract Background Investigating the factors that influence Acinetobacter baumannii (Ab) adhesion/invasion into host cells is important to understand its pathogenicity. Metal cations have been shown to play an important role in regulating the biofilm formation and increasing the virulence of Ab; however, the effects of calcium on host-bacterial interactions have yet to be clarified. Here, the dynamic process of the interactions between Ab and human respiratory epithelial cells and the effects of calcium on host-bacterial interactions were explored using the technologies of microscopic imaging, quantitative PCR and real time cellular analysis (RTCA).Results The concentration of calcium, multiplicity of infection and co-culture time were demonstrated to have effects on host-bacterial interactions. A unique "double peak" phenomenon changed to a sharp "single peak" phenomenon during the process of Ab infection under the effects of calcium were determined based on the time-dependent cell response profiles. Moreover, calcium can increase Ab adhesion/invasion of epithelial cells by regulating the expression of Ab-related genes ( ompA , bfmRS , abaI ).Conclusions Effective control of calcium concentrations can provide new ideas for the prevention and treatment of multi-drug resistant Ab.

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Review: Defensins and cathelicidins in lung immunity

Innate Immunity ◽

10.1177/1753425910365734 ◽

2010 ◽

Vol 16 (3) ◽

pp. 151-159 ◽

Cited By ~ 105

Author(s):

Tesfaldet Tecle ◽

Shweta Tripathi ◽

Kevan L. Hartshorn

Keyword(s):

Epithelial Cells ◽

Immune Responses ◽

Biological Activities ◽

Large Family ◽

Inflammatory Cells ◽

Respiratory Epithelial Cells ◽

Spectrum Activity ◽

Respiratory Epithelial ◽

Lung Immunity

Defensins were first identified in 1985 and are now recognized as part of a large family of antimicrobial peptides, divided into three categories: α-, β-, and θ-defensins. These defensin classes differ in structure, sites of expression and biological activities. Human α-defensins include peptides that are expressed primarily in neutrophils, whereas human β-defensins are widely expressed in epithelial cells, including those lining the respiratory tract. Defensins were first studied for their broad spectrum activity against bacteria, fungi and viruses; however, it is now clear that they also recruit inflammatory cells and promote innate and adaptive immune responses. Recent evidence shows that defensins have anti-inflammatory effects as well. Hence, defensins can participate in all phases of an immune response in the lung, including initial killing of pathogens and mounting — and resolution —- of an immune or inflammatory response. The cathelicidin, LL-37, is an antimicrobial peptide produced by neutrophils and respiratory epithelial cells that has similar roles in lung immunity as the defensins. A major challenge for the coming years will be to sort out the relative contributions of defensins and LL-37 to overall immune responses in the lung and to determine which of their many in vitro activities are most important for lung immunity.

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Preventing the Interaction between Coronaviruses Spike Protein and Angiotensin I Converting Enzyme 2: An In Silico Mechanistic Case Study on Emodin as a Potential Model Compound

Applied Sciences ◽

10.3390/app10186358 ◽

2020 ◽

Vol 10 (18) ◽

pp. 6358

Author(s):

Luca Dellafiora ◽

Jean Lou C M Dorne ◽

Gianni Galaverna ◽

Chiara Dall’Asta

Keyword(s):

Adverse Effects ◽

Antiviral Activity ◽

Model Compound ◽

Biological Activities ◽

Mechanistic Explanation ◽

Host Cells ◽

Spike Protein ◽

Docking Simulations ◽

Functional Conservation ◽

Beneficial Effects

Emodin, a widespread natural anthraquinone, has many biological activities including health-protective and adverse effects. Amongst beneficial effects, potential antiviral activity against coronavirus responsible for the severe acute respiratory syndrome outbreak in 2002–2003 has been described associated with the inhibition of the host cells target receptors recognition by the viral Spike protein. However, the inhibition mechanisms have not been fully characterized, hindering the rational use of emodin as a model compound to develop more effective analogues. This work investigates emodin interaction with the Spike protein to provide a mechanistic explanation of such inhibition. A 3D molecular modeling approach consisting of docking simulations, pharmacophoric analysis and molecular dynamics was used. The plausible mechanism is described as an interaction of emodin at the protein–protein interface which destabilizes the viral protein-target receptor complex. This analysis has been extended to the Spike protein of the coronavirus responsible for the current pandemic hypothesizing emodin’s functional conservation. This solid knowledge-based foothold provides a possible mechanistic rationale of the antiviral activity of emodin as a future basis for the potential development of efficient antiviral cognate compounds. Data gaps and future work on emodin-related adverse effects in parallel to its antiviral pharmacology are explored.

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In Vitro Studies of Mechanisms of Lung Injury in the Rodent

Toxicologic Pathology ◽

10.1177/0192623391019004-111 ◽

1991 ◽

Vol 19 (4_part_1) ◽

pp. 419-427 ◽

Cited By ~ 3

Author(s):

Leah A. Cohn ◽

Kenneth B. Adler

Keyword(s):

Epithelial Cells ◽

Cell Types ◽

Lung Cells ◽

Serum Free Medium ◽

Collagen Gels ◽

Respiratory Epithelial Cells ◽

Respiratory Epithelial ◽

Air Liquid Interface

In order to better define the responses of lung cells to potentially pathogenic insults, primary cell cultures of dissociated respiratory epithelial cells have been established. These epithelial cells have been obtained from various areas of the respiratory tract ranging from the trachea to the alveolus and the cultures have been demonstrated to mimic the differentiated state of these cell types as observed in situ. Several procedures which enhance the differentiated state have been evaluated, which include maintenance on more physiologically-relevant substrata, such as collagen gels, use of defined serum-free medium and use of air/liquid interface systems. These approaches have allowed intracellular responses of respiratory epithelium to toxic insult to be better defined.

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Assessment of Immunity to Mycobacterial Infection with Luciferase Reporter Constructs

Infection and Immunity ◽

10.1128/iai.67.9.4586-4593.1999 ◽

1999 ◽

Vol 67 (9) ◽

pp. 4586-4593 ◽

Cited By ~ 123

Author(s):

Valerie A. Snewin ◽

Marie-Pierre Gares ◽

Peadar ÓGaora ◽

Zahra Hasan ◽

Ivor N. Brown ◽

...

Keyword(s):

Protective Immunity ◽

Rapid Assessment ◽

Cell Types ◽

Mycobacterial Infection ◽

Model Systems ◽

Host Cells ◽

Luciferase Reporter ◽

Simple Alternative ◽

Multiple Cell ◽

Surrogate Measure

ABSTRACT Protective immunity to mycobacterial infection is incompletely understood but probably involves the coordinated interaction of multiple cell types and cytokines. With the aim of developing assays that might provide a surrogate measure of protective immunity, we have investigated the use of recombinant mycobacteria carrying luciferase reporter enzymes to assess the effectiveness of antimycobacterial immunity in model systems. Measurement of luminescence was shown to provide a rapid and simple alternative to the counting of CFU as a means of monitoring mycobacterial viability. We describe optimization of a luciferase reporter strain of Mycobacterium tuberculosis and demonstrate its application for the study of mycobacterial interactions with host cells in tissue culture and the rapid assessment of vaccine efficacy in a murine model.

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Cholesterol enhances cationic liposome-mediated DNA transfection of human respiratory epithelial cells

Bioscience Reports ◽

10.1007/bf01200214 ◽

1995 ◽

Vol 15 (1) ◽

pp. 47-53 ◽

Cited By ~ 42

Author(s):

Michael J. Bennett ◽

Michael H. Nantz ◽

Rajiv P. Balasubramaniam ◽

Dieter C. Gruenert ◽

Robert W. Malone

Keyword(s):

Gene Therapy ◽

Epithelial Cells ◽

Cationic Lipid ◽

Cationic Liposome ◽

Cell Types ◽

Respiratory Epithelial Cells ◽

Cell Monolayers ◽

Dimethyl Ammonium ◽

Human Respiratory Epithelial Cells ◽

Respiratory Epithelial

Cationic liposome transfection reagents are useful for transferring polynucleotides into cells, and have been proposed for human pulmonary gene therapy. The effect of adding cholesterol to cationic lipid preparations has been tested by first formulating the cationic lipid N-[1-(2,3-dioleoyloxy)propyl-N-[1-(2-hydroxy)ethyl]-N,N-dimethyl ammonium iodide (DORI) with varying amounts of dioleoylphos-phatidylethanolamine (DOPE) and cholesterol. Cholesterol was found to enhance lipid-mediated transfection in both the respiratory epithelial cells and mouse fibroblasts. These findings will facilitate nucleic acid transfection of many cell types including differentiated epithelial cell monolayers, and therefore may be useful for examining gene regulation in various cell types and for developing pulmonary gene therapy.

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Effect of Calcium on the Interaction of Acinetobacter baumannii with Human Respiratory Epithelial Cells

10.21203/rs.2.14268/v3 ◽

2019 ◽

Author(s):

Yi Chen ◽

Tingjun Shao ◽

Sanhua Fang ◽

Ping Pan ◽

Jiahui Jiang ◽

...

Keyword(s):

Epithelial Cells ◽

Acinetobacter Baumannii ◽

Host Cells ◽

Effective Control ◽

Respiratory Epithelial Cells ◽

Cellular Analysis ◽

Bacterial Interaction ◽

Dependent Cell ◽

Human Respiratory Epithelial Cells ◽

Respiratory Epithelial

Abstract Background: Investigating the factors that influence Acinetobacter baumannii(Ab) adhesion/invasion of host cells is important to understand its pathogenicity. Metal cations have been shown to play an important role in regulating the biofilm formation and increasing the virulence of Ab; however, the effect of calcium on host-bacterial interaction has yet to be clarified. Here, the dynamic process of the interaction between Ab and human respiratory epithelial cells and the effect of calcium on host-bacterial interaction were explored using microscopic imaging, quantitative PCR and real time cellular analysis (RTCA). Results: The concentration of calcium, multiplicity of infection and co-culture time were all demonstrated to have effects on host-bacterial interaction. A unique "double peak" phenomenon changed to a sharp "single peak" phenomenon during the process of Ab infection under the effect of calcium was observed in the time-dependent cell response profiles. Moreover, calcium can increase Ab adhesion/invasion of epithelial cells by regulating the expression of Ab-related genes (ompA, bfmRS, abaI). Conclusions: Effective control of calcium concentrations can provide new approaches for the prevention and treatment of multi-drug resistant Ab.

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