scholarly journals Large Screening Identifies ACE2 Positively Correlates With NF-κB Signaling Activity and Targeting NF-κB Signaling Drugs Suppress ACE2 Levels

2021 ◽  
Vol 12 ◽  
Author(s):  
Meichen Yan ◽  
Yuan Dong ◽  
Xuena Bo ◽  
Yong Cheng ◽  
Jinbo Cheng
Keyword(s):  
Inflammatory Cytokine ◽  
Library Screening ◽  
Human Cell Lines ◽  
Cytokine Storm ◽  
Converting Enzyme ◽  
Inhibitory Effects ◽  
Angiotensin Converting Enzyme 2 ◽  
Clinical Drugs ◽  
Highly Correlated ◽  
Signaling Activity

Coronaviruses SARS-CoV-2 infected more than 156 million people and caused over 3 million death in the whole world, therefore a better understanding of the underlying pathogenic mechanism and the searching for more effective treatments were urgently needed. Angiotensin-converting enzyme 2 (ACE2) was the receptor for SARS-CoV-2 infection. In this study, we found that ACE2 was an interferon-stimulated gene (ISG) in human cell lines. By performing an ISG library screening, we found that ACE2 levels were positively regulated by multiple ISGs. Interestingly, ACE2 levels were highly correlated with ISGs-induced NF-κB activities, but not IFNβ levels. Furthermore, using an approved clinical durgs library, we found two clinical drugs, Cepharanthine and Glucosamine, significantly inhibited ACE2 level, IFNβ level, and NF-κB signaling downstream TNFα and IL6 levels. Our finding suggested the possible inhibitory effects of Cepharanthine and Glucosamine during SARS-CoV-2 infection and the subsequent inflammatory cytokine storm.

scholarly journals Coronavirus disease 2019: an overview

2021 ◽  
Vol 8 (10) ◽  
pp. 5094
Author(s):  
Ajna Prahalad ◽  
Varun Soti
Keyword(s):  
Mortality Rate ◽  
Literature Search ◽  
Spike Protein ◽  
Cytokine Storm ◽  
Converting Enzyme ◽  
Medical Subject Headings ◽  
Angiotensin Converting Enzyme 2 ◽  
Different Strains ◽  
Vaccine Distribution ◽  
Good Hygiene

Coronavirus disease 2019 (COVID-19) has caused over four million deaths worldwide and continues to affect millions across the globe. This review aims to provide an overview of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the progress made to counter COVID-19 through therapeutics and immunizations. We searched preclinical and clinical COVID-19 literature published between January 2018 through June 2021 on PubMed. The medical subject headings used in the literature search were COVID-19, SARS-CoV-2, Treatment, Remdesivir, Cytokine Storm, Hydroxychloroquine, Epidemiology, Angiotensin-Converting Enzyme 2 Receptor, Vaccines, and Mitigation. There is credible evidence that shows that the spike protein in the SARS-CoV-2’s structure is crucial for the host to be infected. It spreads through different modes, primarily through aerosols and carriers. Pathophysiologically, SARS-CoV-2 triggers a cytokine storm leading to systemic inflammation, which can be fatal. Although treatment with Remdesivir and Dexamethasone and massive vaccinations have significantly reduced the mortality rate, COVID-19 remains a significant threat. The emergence of SARS-CoV-2’s different strains, notably the Delta variant, demonstrates that the COVID-19 pandemic is not over. More vaccine distribution and increased efforts in developing anti-SARS-CoV-2 drugs, social distancing, masking, and practicing good hygiene will be crucial in defeating COVID-19.

scholarly journals Geranium and Lemon Essential Oils and Their Active Compounds Downregulate Angiotensin-Converting Enzyme 2 (ACE2), a SARS-CoV-2 Spike Receptor-Binding Domain, in Epithelial Cells

Plants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 770 ◽  
Author(s):  
K. J. Senthil Kumar ◽  
M. Gokila Vani ◽  
Chung-Shuan Wang ◽  
Chia-Chi Chen ◽  
Yu-Chien Chen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Angiotensin Converting Enzyme ◽  
Essential Oils ◽  
Cell Receptor ◽  
Gas Chromatography Mass Spectrometry ◽  
Converting Enzyme ◽  
Inhibitory Effects ◽  
Angiotensin Converting Enzyme 2 ◽  
Host Cell Receptor ◽  
Lemon Oil

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease-2019 (COVID-19), is a pandemic disease that has been declared as modern history’s gravest health emergency worldwide. Until now, no precise treatment modality has been developed. The angiotensin-converting enzyme 2 (ACE2) receptor, a host cell receptor, has been found to play a crucial role in virus cell entry; therefore, ACE2 blockers can be a potential target for anti-viral intervention. In this study, we evaluated the ACE2 inhibitory effects of 10 essential oils. Among them, geranium and lemon oils displayed significant ACE2 inhibitory effects in epithelial cells. In addition, immunoblotting and qPCR analysis also confirmed that geranium and lemon oils possess potent ACE2 inhibitory effects. Furthermore, the gas chromatography-mass spectrometry (GC–MS) analysis displayed 22 compounds in geranium oil and 9 compounds in lemon oil. Citronellol, geraniol, and neryl acetate were the major compounds of geranium oil and limonene that represented major compound of lemon oil. Next, we found that treatment with citronellol and limonene significantly downregulated ACE2 expression in epithelial cells. The results suggest that geranium and lemon essential oils and their derivative compounds are valuable natural anti-viral agents that may contribute to the prevention of the invasion of SARS-CoV-2/COVID-19 into the human body.

scholarly journals Acalculous Acute Pancreatitis in a COVID-19 Patient

2020 ◽  
Author(s):  
Pedro Antunes Meireles ◽  
Filipe Bessa ◽  
Pedro Gaspar ◽  
Inês Parreira ◽  
Virgílio Dias Silva ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Respiratory Symptoms ◽  
Distress Syndrome ◽  
Cytokine Storm ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Cell Internalization ◽  
Pancreatic Exocrine ◽  
Upper Respiratory ◽  
Upper Respiratory Symptoms

Coronavirus disease 2019 (COVID-19) is a multisystemic condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with manifestations ranging from mild upper respiratory symptoms to cytokine storm causing acute respiratory distress syndrome. Pancreatic exocrine tissue and endocrine islets both express angiotensin-converting enzyme 2 (ACE2), the proven receptor for SARS-CoV-2 cell internalization. An increase in pancreatic enzymes has been increasingly recognized in patients with COVID-19, but little is known about the real prevalence of acute pancreatitis in this population. We report a case of acute acalculous pancreatitis in a COVID-19 patient.

scholarly journals Crosstalk between SARS-CoV-2 and Testicular Hemostasis: Perspective View

2021 ◽  
Author(s):  
R.G. Ahmed
Keyword(s):  
Sexual Behavior ◽  
Sexual Transmission ◽  
Vital Role ◽  
Cytokine Storm ◽  
Converting Enzyme ◽  
Perspective View ◽  
Healthy Life ◽  
Angiotensin Converting Enzyme 2 ◽  
Testicular Dysfunction

The infection of SARS-CoV-2 and its COVID disease caused several economic and social disturbances worldwide. This chapter aimed to determine the severity of SARS-CoV-2 infection on the testicular hemostasis. This overview showed the possible mechanisms of how the SARS-CoV-2 can infect the testes. SARS-CoV-2-induced pneumonia, cytokine storm, and immunosuppressive state may transfer from the respiratory tract to the blood circulation, binding to testicular angiotensin-converting enzyme 2 receptors (ACSE2) and initiate its intracellular replication and action (cytotoxicity), that disrupting the testicular hemostasis. In severe states, COVID-19 disease can increase body/testes temperature, which may destroy the germ cell in the long term. The final mechanism is that SARS-CoV-2 infection causes stress, panic, and anxiety states, causing brain disorders that may perturb the hypothalamic–pituitary-testes-axis (HPTA). This disturbance may then lead to testicular dysfunction. The severity of COVID-19 may be age-dependent and depending on the expression and distribution of testicular ACSE2 receptors. Also, this chapter not only showed the sexual transmission of SARS-CoV-2 but also followed its impact on sexual behavior, pregnancy, and progeny. Thus, maintaining the testicular hemostasis may play a vital role in a healthy life for the offspring. Further research and clinical studies are required to explore this issue.

scholarly journals Gold Metallodrugs to Fight the Corona Virus: Inhibitory Effects on the SpikeACE2 Interaction and on PLpro Protease Activity by Auranofin and Gold Organometallics

2020 ◽  
Author(s):  
Maria Gil-Moles ◽  
Uttara Basu ◽  
Rolf Büssing ◽  
Henrik Hoffmeister ◽  
Sebastian Türck ◽  
...  
Keyword(s):  
Pilot Study ◽  
Viral Entry ◽  
Drug Targets ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Lead Compound ◽  
Inhibitory Effects ◽  
Gold Complexes ◽  
Angiotensin Converting Enzyme 2 ◽  
Key Enzyme

Gold complexes have a long tradition in medicine and for many examples antirheumatic, anticancer or anti-infective effects have been confirmed. Here we evaluated the lead compound Auranofin and five selected gold organometallics as inhibitors of two relevant drug targets of severe acute respiratory syndrome coronaviruses (SARS-CoV). The gold metallodrugs were effective inhibitors of the interaction of the SARS-CoV-2 spike protein with the angiotensin converting enzyme 2 (ACE2) host receptor and might thus interfere with the viral entry process. The gold metallodrugs were also efficient inhibitors of the SARS-CoV-1 papain-like protease (PLpro), which is a key enzyme in the viral replication. Taken together, the results of this pilot study suggest further evaluation of gold complexes as SARS-CoV antiviral drugs.

scholarly journals Gold Metallodrugs to Fight the Corona Virus: Inhibitory Effects on the SpikeACE2 Interaction and on PLpro Protease Activity by Auranofin and Gold Organometallics

2020 ◽  
Author(s):  
Maria Gil-Moles ◽  
Uttara Basu ◽  
Rolf Büssing ◽  
Henrik Hoffmeister ◽  
Sebastian Türck ◽  
...  
Keyword(s):  
Pilot Study ◽  
Viral Entry ◽  
Drug Targets ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Lead Compound ◽  
Inhibitory Effects ◽  
Gold Complexes ◽  
Angiotensin Converting Enzyme 2 ◽  
Key Enzyme

Gold complexes have a long tradition in medicine and for many examples antirheumatic, anticancer or anti-infective effects have been confirmed. Here we evaluated the lead compound Auranofin and five selected gold organometallics as inhibitors of two relevant drug targets of severe acute respiratory syndrome coronaviruses (SARS-CoV). The gold metallodrugs were effective inhibitors of the interaction of the SARS-CoV-2 spike protein with the angiotensin converting enzyme 2 (ACE2) host receptor and might thus interfere with the viral entry process. The gold metallodrugs were also efficient inhibitors of the SARS-CoV-1 papain-like protease (PLpro), which is a key enzyme in the viral replication. Taken together, the results of this pilot study suggest further evaluation of gold complexes as SARS-CoV antiviral drugs.

scholarly journals Management of Patients With Glucocorticoid-Related Diseases and COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Irina Chifu ◽  
Mario Detomas ◽  
Ulrich Dischinger ◽  
Otilia Kimpel ◽  
Felix Megerle ◽  
...  
Keyword(s):  
Adrenal Glands ◽  
Host Cells ◽  
Vulnerable Groups ◽  
Converting Enzyme ◽  
Inhibitory Effects ◽  
Health Crisis ◽  
Angiotensin Converting Enzyme 2 ◽  
Genes Encoding ◽  
Circulating Levels ◽  
Endocrine Tissues

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global health crisis affecting millions of people worldwide. SARS-CoV-2 enters the host cells by binding to angiotensin-converting enzyme 2 (ACE2) after being cleaved by the transmembrane protease serine 2 (TMPRSS2). In addition to the lung, gastrointestinal tract and kidney, ACE2 is also extensively expressed in endocrine tissues, including the pituitary and adrenal glands. Although glucocorticoids could play a central role as immunosuppressants during the cytokine storm, they can have both stimulating and inhibitory effects on immune response, depending on the timing of their administration and their circulating levels. Patients with adrenal insufficiency (AI) or Cushing’s syndrome (CS) are therefore vulnerable groups in relation to COVID-19. Additionally, patients with adrenocortical carcinoma (ACC) could also be more vulnerable to COVID-19 due to the immunosuppressive state caused by the cancer itself, by secreted glucocorticoids, and by anticancer treatments. This review comprehensively summarizes the current literature on susceptibility to and outcome of COVID-19 in AI, CS and ACC patients and emphasizes potential pathophysiological mechanisms of susceptibility to COVID-19 as well as the management of these patients in case of SARS-CoV-2. Finally, by performing an in silico analysis, we describe the mRNA expression of ACE2, TMPRSS2 and the genes encoding their co-receptors CTSB, CTSL and FURIN in normal adrenal and adrenocortical tumors (both adenomas and carcinomas).

Thermodynamics of the interaction between the spike protein of severe acute respiratory syndrome- coronavirus-2 and the receptor of human angiotensin converting enzyme 2. Effects of possible ligands

2020 ◽  
Author(s):  
Cristina Garcia-Iriepa ◽  
Cecilia Hognon ◽  
Antonio Francés-Monerris ◽  
Isabel Iriepa ◽  
Tom Miclot ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Molecular Mechanisms ◽  
Molecular Design ◽  
Binding Free Energy ◽  
Transmembrane Protein ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Rational Molecular Design ◽  
Rational Evaluation

<div><p>Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 180,000 deaths all over the world, still lacking a medical treatment despite the concerns of the whole scientific community. Human Angiotensin-Converting Enzyme 2 (ACE2) was recently recognized as the transmembrane protein serving as SARS-CoV-2 entry point into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the complex and of the effects of possible ligands. Moreover, binding free energy between ACE2 and the active Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is evaluated quantitatively, assessing the molecular mechanisms at the basis of the recognition and the ligand-induced decreased affinity. These results boost the knowledge on the molecular grounds of the SARS-CoV-2 infection and allow to suggest rationales useful for the subsequent rational molecular design to treat severe COVID-19 cases.</p></div>

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