scholarly journals EGCG, a Green Tea Catechin, as a Potential Therapeutic Agent for Symptomatic and Asymptomatic SARS-CoV-2 Infection

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1200
Author(s):  
Mukesh Chourasia ◽  
Purushotham Reddy Koppula ◽  
Aruna Battu ◽  
Madhu M. Ouseph ◽  
Anil K. Singh
Keyword(s):  
Rheumatoid Arthritis ◽  
Epigallocatechin Gallate ◽  
Ubiquitin Proteasome System ◽  
The United States ◽  
Modern World ◽  
Binding Partner ◽  
Inhibitory Function ◽  
Ubiquitin Proteasome ◽  
Green Tea Catechin ◽  
Approved Drugs

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged to be the greatest threat to humanity in the modern world and has claimed nearly 2.2 million lives worldwide. The United States alone accounts for more than one fourth of 100 million COVID-19 cases across the globe. Although vaccination against SARS-CoV-2 has begun, its efficacy in preventing a new or repeat COVID-19 infection in immunized individuals is yet to be determined. Calls for repurposing of existing, approved, drugs that target the inflammatory condition in COVID-19 are growing. Our initial gene ontology analysis predicts a similarity between SARS-CoV-2 induced inflammatory and immune dysregulation and the pathophysiology of rheumatoid arthritis. Interestingly, many of the drugs related to rheumatoid arthritis have been found to be lifesaving and contribute to lower COVID-19 morbidity. We also performed in silico investigation of binding of epigallocatechin gallate (EGCG), a well-known catechin, and other catechins on viral proteins and identified papain-like protease protein (PLPro) as a binding partner. Catechins bind to the S1 ubiquitin-binding site of PLPro, which might inhibit its protease function and abrogate SARS-CoV-2 inhibitory function on ubiquitin proteasome system and interferon stimulated gene system. In the realms of addressing inflammation and how to effectively target SARS-CoV-2 mediated respiratory distress syndrome, we review in this article the available knowledge on the strategic placement of EGCG in curbing inflammatory signals and how it may serve as a broad spectrum therapeutic in asymptomatic and symptomatic COVID-19 patients.

An Updated Review of Disulfiram: Molecular Targets and Strategies for Cancer Treatment

2019 ◽  
Vol 25 (30) ◽  
pp. 3248-3256 ◽  
Author(s):  
Qingzhu Yang ◽  
Yao Yao ◽  
Kai Li ◽  
Lin Jiao ◽  
Jiazhen Zhu ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Anticancer Agents ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Ubiquitin Proteasome System ◽  
Cancer Therapies ◽  
History Of ◽  
Ubiquitin Proteasome ◽  
Delivery Strategies ◽  
Approved Drugs

Repurposing already approved drugs as new anticancer agents is a promising strategy considering the advantages such as low costs, low risks and less time-consumption. Disulfiram (DSF), as the first drug for antialcoholism, was approved by the U.S. Food and Drug Administration (FDA) over 60 years ago. Increasing evidence indicates that DSF has great potential for the treatment of various human cancers. Several mechanisms and targets of DSF related to cancer therapy have been proposed, including the inhibition of ubiquitin-proteasome system (UPS), cancer cell stemness and cancer metastasis, and alteration of the intracellular reactive oxygen species (ROS). This article provides a brief review about the history of the use of DSF in humans and its molecular mechanisms and targets of anticancer therapy, describes DSF delivery strategies for cancer treatment, summarizes completed and ongoing cancer clinical trials involving DSF, and offers strategies to better use DSF in cancer therapies.

scholarly journals Ectromelia Virus Encodes a Novel Family of F-Box Proteins That Interact with the SCF Complex

2008 ◽  
Vol 82 (20) ◽  
pp. 9917-9927 ◽  
Author(s):  
Nick van Buuren ◽  
Brianne Couturier ◽  
Yue Xiong ◽  
Michele Barry
Keyword(s):  
Mass Spectrometry ◽  
Ubiquitin Ligase ◽  
Crucial Role ◽  
Ubiquitin Proteasome System ◽  
Cellular Proteins ◽  
Cowpox Virus ◽  
Ectromelia Virus ◽  
Scf Complex ◽  
Binding Partner ◽  
Ubiquitin Proteasome

ABSTRACT Poxviruses are notorious for encoding multiple proteins that regulate cellular signaling pathways, including the ubiquitin-proteasome system. Bioinformatics indicated that ectromelia virus, the causative agent of lethal mousepox, encoded four proteins, EVM002, EVM005, EVM154, and EVM165, containing putative F-box domains. In contrast to cellular F-box proteins, the ectromelia virus proteins contain C-terminal F-box domains in conjunction with N-terminal ankyrin repeats, a combination that has not been previously reported for cellular proteins. These observations suggested that the ectromelia virus F-box proteins interact with SCF (Skp1, cullin-1, and F-box) ubiquitin ligases. We focused our studies on EVM005, since this protein had only one ortholog in cowpox virus. Using mass spectrometry, we identified cullin-1 as a binding partner for EVM005, and this interaction was confirmed by overexpression of hemagglutinin (HA)-cullin-1. During infection, Flag-EVM005 and HA-cullin-1 colocalized to distinct cellular bodies. Significantly, EVM005 coprecipitated with endogenous Skp1, cullin-1, and Roc1 and associated with conjugated ubiquitin, suggesting that EVM005 interacted with the components of a functional ubiquitin ligase. Interaction of EVM005 with cullin-1 and Skp1 was abolished upon deletion of the F-box, indicating that the F-box played a crucial role in interaction with the SCF complex. Additionally, EVM002 and EVM154 interacted with Skp1 and conjugated ubiquitin, suggesting that ectromelia virus encodes multiple F-box-containing proteins that regulate the SCF complex. Our results indicate that ectromelia virus has evolved multiple proteins that interact with the SCF complex.

scholarly journals Disulfiram as a Therapeutic Agent for Metastatic Malignant Melanoma—Old Myth or New Logos?

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3538
Author(s):  
Francisco Meraz-Torres ◽  
Sarah Plöger ◽  
Claus Garbe ◽  
Heike Niessner ◽  
Tobias Sinnberg
Keyword(s):  
Targeted Therapy ◽  
Molecular Mechanisms ◽  
Tumor Biology ◽  
Ubiquitin Proteasome System ◽  
Metastatic Malignant Melanoma ◽  
Drug Candidate ◽  
Cancer Therapies ◽  
Therapeutic Concepts ◽  
Ubiquitin Proteasome ◽  
Approved Drugs

New therapeutic concepts such as anti-PD-1-based immunotherapy or targeted therapy with BRAF and MEK inhibitors have significantly improved the survival of melanoma patients. However, about 20% of patients with targeted therapy and up to 50% with immunotherapies do not respond to their first-line treatment or rapidly develop resistance. In addition, there is no approved targeted therapy for certain subgroups, namely BRAF wild-type melanomas, although they often bear aggressive tumor biology. A repurposing of already approved drugs is a promising strategy to fill this gap, as it will result in comparatively low costs, lower risks and time savings. Disulfiram (DSF), the first drug to treat alcoholism, which received approval from the US Food and Drug Administration more than 60 years ago, is such a drug candidate. There is growing evidence that DSF has great potential for the treatment of various human cancers, including melanoma. Several mechanisms of its antitumor activity have been identified, amongst them the inhibition of the ubiquitin-proteasome system, the induction of reactive oxygen species and various death signaling pathways. This article provides an overview of the application of DSF in humans, its molecular mechanisms and targets in cancer therapy with a focus on melanoma. The results of clinical studies and experimental combination approaches of DSF with various cancer therapies are discussed, with the aim of exploring the potential of DSF in melanoma therapy.

scholarly journals Trends and Development in Clinical Research of FDA-Approved Drugs Against Interleukin-1β: A Bibliometric Analysis.

2021 ◽  
Author(s):  
Qi Tan ◽  
ZiMo Yang ◽  
Wenjuan Chen ◽  
Yang Jin
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Research ◽  
Bibliometric Analysis ◽  
Clinical Studies ◽  
Inflammatory Diseases ◽  
Hot Spot ◽  
Descriptive Analysis ◽  
The United States ◽  
Approved Drugs ◽  
Fda Approved Drugs

Abstract Background Interleukin(IL)-1β is a promising target for many diseases such as atherosclerosis, rheumatoid arthritis and cancer because it has been found to involve in the development of diseases. Anakinra, Canakinumab and Rilonacept were three Food and Drug Administration (FDA)-approved drugs and used for inhibiting IL-1β. Our study aims to access the trends and development for IL-1β inhibitors using bibliometric analysis. Methods All publication records were obtained from databases Web of Science and Pubmed. Publishing characteristics including organization, author, journals and co-authorship, Keywords, co-occurrence network, related journals network were analyzed by VOSviewer 1.6.16 (by Leiden University) and Bibliometric package in R(4.0.5). Graph prism 8 was used to performed descriptive analysis of all data. Results 274 publications were enrolled in our study. Of the three drugs, anakinra has been extensively studied, with 130 publications related to it between 1997 and 2021. Clinical studies on IL-1β antagonists mainly focused on rheumatoid arthritis. Non-inflammatory diseases such as cardiovascular disease and cancer were also found in the related clinical research. The United States published the most articles in clinical research on IL-1β inhibitor and it was the country that participated in the most collaborations. Conclusion Targeting IL-1β was still a hot spot for clinical research in inflammatory diseases. As progresses are made in the field, Canakinumab and Rilonocept as two novel inhibitors, will increase in a similar trend to that of Anakinra. The number of studies about the inhibitors targeting IL-1β in inflammatory diseases will emerge more in the future. Cancer therapy might be the trend in the clinical studies of antagonizing IL-1β.

Fenofibrate, a PPARα agonist, decreases atrogenes and myostatin expression and improves arthritis-induced skeletal muscle atrophy

2011 ◽  
Vol 300 (5) ◽  
pp. E790-E799 ◽  
Author(s):  
Estíbaliz Castillero ◽  
María Paz Nieto-Bona ◽  
Carmen Fernández-Galaz ◽  
Ana Isabel Martín ◽  
María López-Menduiña ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Ubiquitin Proteasome System ◽  
Skeletal Muscle Atrophy ◽  
Skeletal Muscle Wasting ◽  
Cross Section Area ◽  
Section Area ◽  
Ubiquitin Proteasome ◽  
Injection Control

Arthritis is a chronic inflammatory illness that induces cachexia, which has a direct impact on morbidity and mortality. Fenofibrate, a selective PPARα activator prescribed to treat human dyslipidemia, has been reported to decrease inflammation in rheumatoid arthritis patients. The aim of this study was to elucidate whether fenofibrate is able to ameliorate skeletal muscle wasting in adjuvant-induced arthritis, an experimental model of rheumatoid arthritis. On day 4 after adjuvant injection, control and arthritic rats were treated with 300 mg/kg fenofibrate until day 15, when all rats were euthanized. Fenofibrate decreased external signs of arthritis and liver TNFα and blocked arthritis-induced decreased in PPARα expression in the gastrocnemius muscle. Arthritis decreased gastrocnemius weight, which results from a decrease in cross-section area and myofiber size, whereas fenofibrate administration to arthritic rats attenuated the decrease in both gastrocnemius weight and fast myofiber size. Fenofibrate treatment prevented arthritis-induced increase in atrogin-1 and MuRF1 expression in the gastrocnemius. Neither arthritis nor fenofibrate administration modify Akt-FoxO3 signaling. Myostatin expression was not modified by arthritis, but fenofibrate decreased myostatin expression in the gastrocnemius of arthritic rats. Arthritis increased muscle expression of MyoD, PCNA, and myogenin in the rats treated with vehicle but not in those treated with fenofibrate. The results indicate that, in experimental arthritis, fenofibrate decreases skeletal muscle atrophy through inhibition of the ubiquitin-proteasome system and myostatin.

The ubiquitin–proteasome system and skeletal muscle wasting

2005 ◽  
Vol 41 ◽  
pp. 173-186 ◽  
Author(s):  
Didier Attaix ◽  
Sophie Ventadour ◽  
Audrey Codran ◽  
Daniel Béchet ◽  
Daniel Taillandier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Wasting ◽  
Proteolytic Enzymes ◽  
Cathepsin L ◽  
Ubiquitin Proteasome System ◽  
Complete Breakdown ◽  
Skeletal Muscle Proteins ◽  
Ubiquitin Proteasome ◽  
Tripeptidyl Peptidase Ii ◽  
F Box Protein

The ubiquitin–proteasome system (UPS) is believed to degrade the major contractile skeletal muscle proteins and plays a major role in muscle wasting. Different and multiple events in the ubiquitination, deubiquitination and proteolytic machineries are responsible for the activation of the system and subsequent muscle wasting. However, other proteolytic enzymes act upstream (possibly m-calpain, cathepsin L, and/or caspase 3) and downstream (tripeptidyl-peptidase II and aminopeptidases) of the UPS, for the complete breakdown of the myofibrillar proteins into free amino acids. Recent studies have identified a few critical proteins that seem necessary for muscle wasting {i.e. the MAFbx (muscle atrophy F-box protein, also called atrogin-1) and MuRF-1 [muscle-specific RING (really interesting new gene) finger 1] ubiquitin–protein ligases}. The characterization of their signalling pathways is leading to new pharmacological approaches that can be useful to block or partially prevent muscle wasting in human patients.

The ubiquitin–proteasome system and skeletal muscle wasting

2005 ◽  
Vol 41 (1) ◽  
pp. 173 ◽  
Author(s):  
Didier Attaix ◽  
Sophie Ventadour ◽  
Audrey Codran ◽  
Daniel Béchet ◽  
Daniel Taillandier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Wasting ◽  
Ubiquitin Proteasome System ◽  
Skeletal Muscle Wasting ◽  
Ubiquitin Proteasome
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