scholarly journals Molecular profiling of Neprilysin expression and its interactions with SARS-CoV-2 spike proteins to develop evidence base pharmacological approaches for therapeutic intervention

2021 ◽  
Author(s):  
Arun Kumar
Keyword(s):  
Molecular Docking ◽  
Potential Role ◽  
Sequence Similarity ◽  
Evidence Base ◽  
Molecular Profile ◽  
Peptidase Activity ◽  
Significant Sequence Similarity ◽  
Angiotensin Converting Enzyme 2 ◽  
Proteins Interactions

Abstract Neprilysin due to its peptidase activity is involved in several physiological and pathological processes. Recently our group has reported the association of neprilysin with angiotensin-converting enzyme 2 (ACE2) network proteins which facilitate the entry of SARS-COV2 virus. The potential role of neprilysin beyond its peptidase activity is not known. Using the established sequence analysis and molecular docking tools, this study evaluated the molecular profile of neprilysin interaction with SARS-COV2 virus proteins. Human neprilysin protein showed a significant sequence similarity with SARS-COV2 spike protein, which was further confirmed by observation of considerable interaction in the molecular docking. Human neprilysin protein was also found to additionally interact with SARS-COV2 proteins facilitating virus replication. The potential of neprilysin inhibitors (Sacubitril and Sacubitrilat) to interfere with neprilysin and SARS-COV2 proteins interactions was assessed. The neprilysin inhibitors showed binding efficacy within therapeutically feasible concentration range (1 to 150 uM). This study while reporting a novel role of neprilysin as potential receptor for SARS-COV2 virus, highlights the merit in assessing clinical efficacy of neprilysin inhibitors for the management of SARS-COV2 infection.

scholarly journals Gut microbiota influence in type 2 diabetes mellitus (T2DM)

Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
A. L. Cunningham ◽  
J. W. Stephens ◽  
D. A. Harris
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Gut Microbiota ◽  
Potential Role ◽  
Evidence Base ◽  
Human Metabolism ◽  
Altered Glucose

AbstractA strong and expanding evidence base supports the influence of gut microbiota in human metabolism. Altered glucose homeostasis is associated with altered gut microbiota, and is clearly associated with the development of type 2 diabetes mellitus (T2DM) and associated complications. Understanding the causal association between gut microbiota and metabolic risk has the potential role of identifying susceptible individuals to allow early targeted intervention.

scholarly journals Legionella pneumophila CRISPR-Cas suggests recurrent encounters with one or more phages in the family Microviridae .

2021 ◽  
Author(s):  
Shayna R. Deecker ◽  
Malene L. Urbanus ◽  
Beth Nicholson ◽  
Alexander W. Ensminger
Keyword(s):  
Legionella Pneumophila ◽  
Sequence Similarity ◽  
Mobile Element ◽  
Current Data ◽  
Significant Sequence Similarity ◽  
Remediation Strategies ◽  
The Family ◽  
Legionnaires Disease ◽  
Outstanding Question

Legionella pneumophila is a ubiquitous freshwater pathogen and the causative agent of Legionnaires’ disease. L. pneumophila growth within protists provides a refuge from desiccation, disinfection, and other remediation strategies. One outstanding question has been whether this protection extends to phages. L. pneumophila isolates are remarkably devoid of prophages and to date no Legionella phages have been identified. Nevertheless, many L. pneumophila isolates maintain active CRISPR-Cas defenses. So far, the only known target of these systems is an episomal element that we previously named Legionella Mobile Element-1 (LME-1). The continued expansion of publicly available genomic data promises to further our understanding of the role of these systems. We now describe over 150 CRISPR-Cas systems across 600 isolates to establish the clearest picture yet of L. pneumophila ’s adaptive defenses. By searching for targets of 1,500 unique CRISPR-Cas spacers, LME-1 remains the only identified CRISPR-Cas targeted integrative element. We identified 3 additional LME-1 variants - all targeted by previously and newly identified CRISPR-Cas spacers - but no other similar elements. Notably, we also identified several spacers with significant sequence similarity to microviruses, specifically those within the subfamily Gokushovirinae . These spacers are found across several different CRISPR-Cas arrays isolated from geographically diverse isolates, indicating recurrent encounters with these phages. Our analysis of the extended Legionella CRISPR-Cas spacer catalog leads to two main conclusions: current data argue against CRISPR-Cas targeted integrative elements beyond LME-1, and the heretofore unknown L. pneumophila phages are most likely lytic gokushoviruses. IMPORTANCE Legionnaires’ disease is an often-fatal pneumonia caused by Legionella pneumophila , which normally grows inside amoebae and other freshwater protists. L. pneumophila trades diminished access to nutrients for the protection and isolation provided by the host. One outstanding question is whether L. pneumophila is susceptible to phages, given the protection provided by its intracellular lifestyle. In this work, we use Legionella CRISPR spacer sequences as a record of phage infection to predict that the “missing” L. pneumophila phages belong to the microvirus subfamily Gokushovirinae . Gokushoviruses are known to infect another intracellular pathogen, Chlamydia . How do gokushoviruses access L. pneumophila (and Chlamydia ) inside their “cozy niches”? Does exposure to phages happen during a transient extracellular period (during cell-to-cell spread) or is it indicative of a more complicated environmental lifestyle? One thing is clear, 100 years after their discovery, phages continue to hold important secrets about the bacteria upon which they prey.

scholarly journals Is There a Link between Bisphenol A (BPA), a Key Endocrine Disruptor, and the Risk for SARS-CoV-2 Infection and Severe COVID-19?

2020 ◽  
Vol 9 (10) ◽  
pp. 3296
Author(s):  
Aeman Zahra ◽  
Cristina Sisu ◽  
Elisabete Silva ◽  
Sophie-Christine De Aguiar Greca ◽  
Harpal S. Randeva ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Potential Role ◽  
Metabolic Diseases ◽  
Endocrine Disrupting Chemicals ◽  
Angiotensin Converting Enzyme 2 ◽  
Endocrine Disrupting ◽  
Membrane Bound ◽  
Transmembrane Serine Protease ◽  
G Protein Coupled

Infection by the severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) is the causative agent of a new disease (COVID-19). The risk of severe COVID-19 is increased by certain underlying comorbidities, including asthma, cancer, cardiovascular disease, hypertension, diabetes, and obesity. Notably, exposure to hormonally active chemicals called endocrine-disrupting chemicals (EDCs) can promote such cardio-metabolic diseases, endocrine-related cancers, and immune system dysregulation and thus, may also be linked to higher risk of severe COVID-19. Bisphenol A (BPA) is among the most common EDCs and exerts its effects via receptors which are widely distributed in human tissues, including nuclear oestrogen receptors (ERα and ERβ), membrane-bound oestrogen receptor (G protein-coupled receptor 30; GPR30), and human nuclear receptor oestrogen-related receptor gamma. As such, this paper focuses on the potential role of BPA in promoting comorbidities associated with severe COVID-19, as well as on potential BPA-induced effects on key SARS-CoV-2 infection mediators, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Interestingly, GPR30 appears to exhibit greater co-localisation with TMPRSS2 in key tissues like lung and prostate, suggesting that BPA exposure may impact on the local expression of these SARS-CoV-2 infection mediators. Overall, the potential role of BPA on the risk and severity of COVID-19 merits further investigation.

scholarly journals Prior Routine Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Important Outcomes in Hospitalised Patients with COVID-19

2020 ◽  
Vol 9 (8) ◽  
pp. 2586 ◽  
Author(s):  
Eilidh Bruce ◽  
Fenella Barlow-Pay ◽  
Roxanna Short ◽  
Arturo Vilches-Moraga ◽  
Angeline Price ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Severe Acute Respiratory Syndrome ◽  
Observational Study ◽  
Potential Role ◽  
Multivariable Analysis ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Hospitalised Patients ◽  
Inflammatory Drugs

Coronavirus disease 2019 (COVID-19) infection causes acute lung injury, resulting from aggressive inflammation initiated by viral replication. There has been much speculation about the potential role of non-steroidal inflammatory drugs (NSAIDs), which increase the expression of angiotensin-converting enzyme 2 (ACE2), a binding target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter the host cell, which could lead to poorer outcomes in COVID-19 disease. The aim of this study was to examine the association between routine use of NSAIDs and outcomes in hospitalised patients with COVID-19. This was a multicentre, observational study, with data collected from adult patients with COVID-19 admitted to eight UK hospitals. Of 1222 patients eligible to be included, 54 (4.4%) were routinely prescribed NSAIDs prior to admission. Univariate results suggested a modest protective effect from the use of NSAIDs, but in the multivariable analysis, there was no association between prior NSAID use and time to mortality (adjusted HR (aHR) = 0.89, 95% CI 0.52–1.53, p = 0.67) or length of stay (aHR 0.89, 95% CI 0.59–1.35, p = 0.58). This study found no evidence that routine NSAID use was associated with higher COVID-19 mortality in hospitalised patients; therefore, patients should be advised to continue taking these medications until further evidence emerges. Our findings suggest that NSAID use might confer a modest benefit with regard to survival. However, as this finding was underpowered, further research is required.

scholarly journals Endocrine Significance of SARS-CoV-2’s Reliance on ACE2

Endocrinology ◽  
2020 ◽  
Vol 161 (9) ◽  
Author(s):  
Eric Lazartigues ◽  
Mirza Muhammad Fahd Qadir ◽  
Franck Mauvais-Jarvis
Keyword(s):  
Potential Role ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Global Impact ◽  
The Past ◽  
And Function ◽  
Endocrine Tissues

Abstract The current COVID-19 pandemic is the most disruptive event in the past 50 years, with a global impact on health care and world economies. It is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a coronavirus that uses angiotensin-converting enzyme 2 (ACE2) as an entry point to the cells. ACE2 is a transmembrane carboxypeptidase and member of the renin-angiotensin system. This mini-review summarizes the main findings regarding ACE2 expression and function in endocrine tissues. We discuss rapidly evolving knowledge on the potential role of ACE2 and SARS coronaviruses in endocrinology and the development of diabetes mellitus, hypogonadism, and pituitary and thyroid diseases.

scholarly journals Confronting the potential role of Yoga in the molecular profile of rural high-risk women for Diabetes: a pilot study

2021 ◽  
Vol 2 (2) ◽  
pp. 38
Author(s):  
Navneet Kaur ◽  
Shweta Ahuja ◽  
Kanupriya Sharma ◽  
Rakesh Malik ◽  
Kavita Bakshi ◽  
...  
Keyword(s):  
Pilot Study ◽  
High Risk ◽  
Rural Women ◽  
Potential Role ◽  
Cellular Growth ◽  
Molecular Profile ◽  
High Risk Women ◽  
Beneficial Impact ◽  
The Mind

Background and purpose: Yoga has been shown to have established beneficial impact through many previous studies. The mind-body practices like Yoga have an ameliorating effect on diabetes and prediabetes. The majority of prior published literature focused their attention on the glucose parameters in diabetic and prediabetic pathology. The purpose of the present pilot study is to explore the effect of AYUSH-approved Diabetic Yoga Protocol (DYP) on selected angiogenesis and neurogenesis markers in high-risk rural women for Diabetes. Methods: Total 15 high-risk women for Diabetes were selected from rural area of Chandigarh, for a 3-month DYP intervention. The pre-post single group experimental research design was implemented in the study. The changes in angiogenesis, neurogenesis parameters, and leptin were assessed at baseline and after 3 months after DYP intervention. Results: The result of the present study revealed that after 3 months of DYP intervention the statistically significant improvements were noticed on serum VEGF levels (p = 0.039). The improvements in angiogenin and BDNF levels were also seen after DYP practice. Conclusion: The results highlight the potential role of DYP on cellular growth and neuronal survival. Keywords: Diabetic Yoga Protocol, Indian Diabetes Risk Score, Prediabetes, angiogenesis, neurogenesis.

scholarly journals Potential Role of Antioxidant and Anti-Inflammatory Therapies to Prevent Severe SARS-Cov-2 Complications

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 272
Author(s):  
Anna M. Fratta Pasini ◽  
Chiara Stranieri ◽  
Luciano Cominacini ◽  
Chiara Mozzini
Keyword(s):  
Potential Role ◽  
Viral Infections ◽  
Host Cells ◽  
Nuclear Factor ◽  
Angiotensin Converting Enzyme 2 ◽  
Pyrin Domain ◽  
Nrf2 Activation ◽  
Anti Inflammatory ◽  
Receptor Family

The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2). Here, we review the molecular pathogenesis of SARS-CoV-2 and its relationship with oxidative stress (OS) and inflammation. Furthermore, we analyze the potential role of antioxidant and anti-inflammatory therapies to prevent severe complications. OS has a potential key role in the COVID-19 pathogenesis by triggering the NOD-like receptor family pyrin domain containing 3 inflammasome and nuclear factor-kB (NF-kB). While exposure to many pro-oxidants usually induces nuclear factor erythroid 2 p45-related factor2 (NRF2) activation and upregulation of antioxidant related elements expression, respiratory viral infections often inhibit NRF2 and/or activate NF-kB pathways, resulting in inflammation and oxidative injury. Hence, the use of radical scavengers like N-acetylcysteine and vitamin C, as well as of steroids and inflammasome inhibitors, has been proposed. The NRF2 pathway has been shown to be suppressed in severe SARS-CoV-2 patients. Pharmacological NRF2 inducers have been reported to inhibit SARS-CoV-2 replication, the inflammatory response, and transmembrane protease serine 2 activation, which for the entry of SARS-CoV-2 into the host cells through the angiotensin converting enzyme 2 receptor. Thus, NRF2 activation may represent a potential path out of the woods in COVID-19 pandemic.

scholarly journals Diabetic Nephropathy and COVID-19: The Potential Role of Immune Actors

2021 ◽  
Vol 22 (15) ◽  
pp. 7762
Author(s):  
Diane Mourad ◽  
Nadim S. Azar ◽  
Sami T. Azar
Keyword(s):  
Diabetic Nephropathy ◽  
Viral Entry ◽  
Type Ii Diabetes ◽  
Potential Role ◽  
Underlying Mechanism ◽  
Type Ii Diabetes Mellitus ◽  
Angiotensin Converting Enzyme 2 ◽  
Neuropilin 1 ◽  
Mitochondrial Glutathione

Nowadays, type II diabetes mellitus, more specifically ensuing diabetic nephropathy, and severe COVID-19 disease are known to be closely associated. The exact mechanisms behind this association are less known. An implication for the angiotensin-converting enzyme 2 remains controversial. Some researchers have started looking into other potential actors, such as neuropilin-1, mitochondrial glutathione, vitamin D, and DPP4. In particular, neuropilin-1 seems to play an important role in the underlying mechanism linking COVID-19 and diabetic nephropathy. We suggest, based on the findings in this review, that its up-regulation in the diabetic kidney facilitates viral entry in this tissue, and that the engagement of both processes leads to a depletion of neuropilin-1, which was demonstrated to be strongly associated with the pathogenesis of DN. More studies are needed to confirm this hypothesis, and research should be directed towards elucidating the potential roles of all these suggested actors and eventually discovering new therapeutic strategies that could reduce the burden of COVID-19 in patients with diabetic nephropathy.

scholarly journals Potential role of medicinal plants and their constituents in the mitigation of SARS-CoV-2: identifying related therapeutic targets using network pharmacology and molecular docking analyses

RSC Advances ◽  
2020 ◽  
Vol 10 (47) ◽  
pp. 27961-27983 ◽  
Author(s):  
Eman Shawky ◽  
Ahmed A. Nada ◽  
Reham S. Ibrahim
Keyword(s):  
Molecular Docking ◽  
Medicinal Plants ◽  
Supportive Care ◽  
Management Strategy ◽  
Potential Role ◽  
Network Pharmacology ◽  
Current Management ◽  
Antiviral Medication ◽  
Current Management Strategy

Since the outbreak of Coronavirus disease (COVID-19) caused by SARS-CoV-2 in December 2019, there has been no vaccine or specific antiviral medication for treatment of the infection where supportive care and prevention of complications is the current management strategy.

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