scholarly journals Evidence that Maackia amurensis seed lectin (MASL) exerts pleiotropic actions on oral squamous cells to inhibit SARS-CoV-2 infection and COVID-19 disease progression

2020 ◽  
Author(s):  
Stephanie A. Sheehan ◽  
Kelly L. Hamilton ◽  
Edward P. Retzbach ◽  
Premalatha Balachandran ◽  
Harini Krishnan ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Antiviral Agent ◽  
Host Cells ◽  
Spike Protein ◽  
Host Interactions ◽  
Squamous Cells ◽  
Oral Epithelial Cells ◽  
Maackia Amurensis ◽  
Oral Epithelial ◽  
Pleiotropic Actions

Abstract COVID-19 was declared an international public health emergency in January, and a pandemic in March of 2020. There are over 23 million confirmed COVID-19 cases that have cause over 800 thousand deaths worldwide as of August 19th, 2020. COVID-19 is caused by the SARS-CoV-2 virus. SARS-CoV-2 presents a surface “spike” protein that binds to the ACE2 receptor to infect host cells. In addition to the respiratory tract, SARS-Cov-2 can also infect cells of the oral mucosa, which also express the ACE2 receptor. The spike and ACE2 proteins are highly glycosylated with sialic acid modifications that direct viral-host interactions and infection. Maackia amurensis seed lectin (MASL) has a strong affinity for sialic acid modified proteins and can be used as an antiviral agent. Here, we report that MASL targets the ACE2 receptor, decreases ACE2 expression and glycosylation, suppresses binding of the SARS-CoV-2 spike protein, and decreases expression of inflammatory mediators by oral epithelial cells that cause ARDS in COVID-19 patients. This work identifies MASL as an agent with potential to inhibit SARS-CoV-2 infection and COVID-19 related inflammatory syndromes.

scholarly journals Role of Neuraminidase-Producing Bacteria in Exposing Cryptic Carbohydrate Receptors forStreptococcus gordoniiAdherence

2018 ◽  
Vol 86 (7) ◽  
pp. e00068-18 ◽  
Author(s):  
Alex Wong ◽  
Margaret A. Grau ◽  
Anirudh K. Singh ◽  
Shireen A. Woodiga ◽  
Samantha J. King
Keyword(s):  
Sialic Acid ◽  
Oral Cavity ◽  
Bacterial Species ◽  
Dependent Manner ◽  
Neuraminidase Treatment ◽  
Content Type ◽  
Oral Epithelial Cells ◽  
Oral Environment ◽  
Oral Epithelial

ABSTRACTStreptococcus gordoniiis an early colonizer of the oral cavity. Although a variety ofS. gordoniiadherence mechanisms have been described, current dogma is that the major receptor forS. gordoniiis sialic acid. However, as many bacterial species in the oral cavity produce neuraminidase that can cleave terminal sialic acid, it is unclear whetherS. gordoniirelies on sialic acid for adherence to oral surfaces or if this species has developed alternative binding strategies. Previous studies have examined adherence to immobilized glycoconjugates and identified binding to additional glycans, but no prior studies have defined the contribution of these different glycan structures in adherence to oral epithelial cells. We determined that the majority ofS. gordoniistrains tested did not rely on sialic acid for efficient adherence. In fact, adherence of some strains was significantly increased following neuraminidase treatment. Further investigation of representative strains that do not rely on sialic acid for adherence revealed binding not only to sialic acid via the serine-rich repeat protein GspB but also to β-1,4-linked galactose. Adherence to this carbohydrate occurs via an unknown adhesin distinct from those utilized byStreptococcus oralisandStreptococcus pneumoniae. Demonstrating the potential biological relevance of binding to this cryptic receptor, we established thatS. oralisincreasesS. gordoniiadherence in a neuraminidase-dependent manner. These data suggest thatS. gordoniihas evolved to simultaneously utilize both terminal and cryptic receptors in response to the production of neuraminidase by other species in the oral environment.

scholarly journals Effects of Oral Commensal Streptococci on Porphyromonas gingivalis Invasion into Oral Epithelial Cells

2020 ◽  
Vol 8 (2) ◽  
pp. 39 ◽  
Author(s):  
Alyssa N. Hanel ◽  
Hannah M. Herzog ◽  
Michelle G. James ◽  
Giancarlo A. Cuadra
Keyword(s):  
Epithelial Cells ◽  
Porphyromonas Gingivalis ◽  
Commensal Bacteria ◽  
Host Cells ◽  
Protective Effects ◽  
Trypan Blue Exclusion ◽  
Oral Epithelial Cells ◽  
Commensal Species ◽  
Before And After ◽  
Oral Epithelial

The objective of this study was to determine if the interaction between common oral commensal bacteria and oral epithelial cells would provide protective effects against the invasion of periodontopathogen Porphyromonas gingivalis. Oral epithelial OKF6/Tert cells were used in co-cultures with Streptococcus gordonii, Streptococcus oralis, Streptococcus mitis, and Streptococcus intermedius. The viability of OKF6/Tert cells following a bacterial challenge was evaluated by trypan blue exclusion. The adherence of commensal species was determined by CFU counts. P. gingivalis invasion in OKF6/Tert cells was assessed before and after exposure to commensal species according to CFU counts. Viability assays show that only S. gordonii and S. intermedius display low toxicity toward OKF6/Tert cells. Both commensals adhere to OKF6/Tert cells at an average ratio of 1 CFU to 10 cells. P. gingivalis invasion into host cells is significantly reduced by 25% or 60% after exposure to S. gordonii or S. intermedius, respectively. The results suggest that these commensal species bind to host cells and diminish P. gingivalis invasion. This is important in the context of periodontal disease since P. gingivalis primarily acts on the host by invading it. Therefore, efforts to decrease invasion will eventually lead to future therapies harnessing the mechanisms employed by oral commensal bacteria.

scholarly journals Identification of Potential Binding Sites of Sialic Acids on the RBD Domain of SARS-CoV-2 Spike Protein

2021 ◽  
Vol 9 ◽  
Author(s):  
Bingqian Li ◽  
Lin Wang ◽  
Huan Ge ◽  
Xianglei Zhang ◽  
Penxuan Ren ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Binding Sites ◽  
Sialic Acids ◽  
Host Cells ◽  
Spike Protein ◽  
Molecular Probe ◽  
Acetylneuraminic Acid ◽  
Mass Spectrum Analysis ◽  
Multiple Receptors ◽  
Potential Binding

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still an emergent pandemic for humans. The virus infection is achieved by penetrating its spike protein to host cells via binding with ACE2. Moreover, recent studies show that SARS-CoV-2 may have multiple receptors that need to be further revealed. SARS-CoV-2 shares similar sequences of the spike protein with the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which can invade host cells by binding to either DPP4 or sialic acids. Sialic acids can be linked to the terminal of glycoproteins and gangliosides are used as one of the receptors of many types of viruses. Therefore, it is very interesting to determine whether sialic acid is a potential receptor of SARS-CoV-2. To address this question, we took N-Acetylneuraminic acid (Neu5Ac), a type of predominant sialic acid found in human cells, as the molecular probe to computationally search the surface of the spike protein to locate the potential binding sites of Neu5Ac. SPR analysis and mass spectrum analysis confirmed the interaction between Neu5Ac and spike protein. This study shows that sialic acids can moderately interact with the spike protein of SARS-CoV-2 by binding between the two RBDs of the spike protein, indicating it could be a potential secondary or auxiliary receptor of SARS-CoV-2.

scholarly journals Candida albicans Secreted Aspartic Protease 7 is Essential for Damage of Human Oral Epithelial Cells

2021 ◽  
Vol 8 (5) ◽  
Author(s):  
Yang HP ◽  
◽  
Tsang PCS ◽  
Pow EHN ◽  
Lam OLT ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Epithelial Cells ◽  
Mutant Strain ◽  
Tissue Damage ◽  
Wide Spectrum ◽  
Host Cells ◽  
Wild Type ◽  
Oral Epithelial Cells ◽  
Disruption Method ◽  
Oral Epithelial

Aims: Candida albicans is an important human fungal pathogen in clinical settings. It possesses a wide spectrum of virulence traits, including but not limited to the production of Secreted Aspartic Proteases (SAPs), to invade host cells under predisposing conditions. The aims of the present study were to investigate the functional role of C. albicans SAP7 in invasion ability. Methods: The present study was carried out to construct C. albicans sap7Δ/Δ mutant strain using a PCR-based gene disruption method. The behaviors of this SAP7 knockout strain was evaluated and compared with the wild type and SAP7 complemented strains between human oral epithelial cells with respect to endocytosis, invasion, and tissue damage. Results: Compared with the wild type C. albicans strain, a 52% reduction in the endocytosis of the sap7Δ/Δ mutant strain by oral epithelial cells was observed, as well as a 25% attenuation of internalization, and a 27% reduction of tissue damage (P<0.05). Conclusion: Our data clearly demonstrates that C. albicans SAP7 contributes to tissue invasion into human oral epithelial cells which warrant further investigations as potential targets for antifungal interventions.

scholarly journals The Globular C1q Receptor Is Required for Epidermal Growth Factor Receptor Signaling during Candida albicans Infection

mBio ◽  
2021 ◽  
Author(s):  
Quynh T. Phan ◽  
Jianfeng Lin ◽  
Norma V. Solis ◽  
Michael Eng ◽  
Marc Swidergall ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Host Cells ◽  
Oropharyngeal Candidiasis ◽  
Content Type ◽  
Oral Epithelial Cells ◽  
Cytokines And Chemokines ◽  
Epidermal Growth ◽  
Growth Factor Receptor Signaling ◽  
Candida Albicans Infection ◽  
Oral Epithelial

Oral epithelial cells play a key role in the pathogenesis of oropharyngeal candidiasis. In addition to being target host cells for C. albicans adherence and invasion, they secrete proinflammatory cytokines and chemokines that recruit T cells and activated phagocytes to foci of infection.

scholarly journals Binding of the SARS-CoV-2 Spike Protein to Glycans

2020 ◽  
Author(s):  
Wei Hao ◽  
Bo Ma ◽  
Ziheng Li ◽  
Xiaoyu Wang ◽  
Xiaopan Gao ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Antiviral Agents ◽  
Critical Factor ◽  
Host Cells ◽  
Spike Protein ◽  
General Mechanism ◽  
Dependent Manner ◽  
Potential Importance ◽  
The World ◽  
S Proteins

AbstractThe pandemic of SARS-CoV-2 has caused a high number of deaths in the world. To combat it, it is necessary to develop a better understanding of how the virus infects host cells. Infection normally starts with the attachment of the virus to cell-surface glycans like heparan sulfate (HS) and sialic acid-containing oligosaccharides. In this study, we examined and compared the binding of the subunits and spike (S) proteins of SARS-CoV-2 and SARS-CoV, MERS-CoV to these glycans. Our results revealed that the S proteins and subunits can bind to HS in a sulfation-dependent manner, the length of HS is not a critical factor for the binding, and no binding with sialic acid residues was detected. Overall, this work suggests that HS binding may be a general mechanism for the attachment of these coronaviruses to host cells, and supports the potential importance of HS in infection and in the development of antiviral agents against these viruses.

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