Sugar-Derived Amidines and Congeners: Structures, Glycosidase Inhibition and Applications

2021 ◽  
Vol 29 ◽  
Author(s):  
Yves Blériot ◽  
Nicolas Auberger ◽  
Jérôme Désiré
Keyword(s):  
Transition State ◽  
Chemical Stability ◽  
Viral Infections ◽  
Glycosidic Bond ◽  
Lysosomal Storage ◽  
Research Groups ◽  
Vast Array ◽  
Transition State Analogs ◽  
The World

Abstract: Glycosidases, the enzymes responsible for the breakdown of glycoconjugates including di-, oligo- and polysaccharides are ubiquitous through all kingdoms of life. The extreme chemical stability of the glycosidic bond combined with the catalytic rates achieved by glycosidases makes them among the most proficient of all enzymes. 
 Given their multitude of roles in vivo, inhibition of these enzymes is highly attractive with potential in the treatment of a vast array of pathologies ranging from lysosomal storage and diabetes to viral infections. Therefore great efforts have been invested in the last three decades to design and synthesize inhibitors of glycosidases leading to a number of drugs currently on the market. Amongst the vast array of structures that have been disclosed, sugars incorporating an amidine moiety have been the focus of many research groups around the world because of their glycosidase transition state-like structure. In this review we report and discuss the structure, the inhibition profile and the use of these molecules including related structural congeners as transition state analogs.

scholarly journals The limitations of in vitro experimentation in understanding biofilms and chronic infection

2015 ◽  
Author(s):  
Aled E L Roberts ◽  
Kasper N Kragh ◽  
Thomas Bjarnsholt ◽  
Stephen P Diggle
Keyword(s):  
Chronic Infection ◽  
Pathogenic Bacteria ◽  
Research Groups ◽  
Microtitre Plate ◽  
Chronic Infections ◽  
Flow Cells ◽  
In Vitro Methods ◽  
The World

We have become increasingly aware that during infection, pathogenic bacteria often grow in multicellular biofilms which are often highly resistant to antibacterial strategies. In order to understand how biofilms form and contribute to infection, in vitro biofilm systems such as microtitre plate assays and flow cells, have been heavily used by many research groups around the world. Whilst these methods have greatly increased our understanding of the biology of biofilms, it is becoming increasingly apparent that many of our in vitro methods do not accurately represent in vivo conditions. Here we present a systematic review of the most widely used in vitro biofilm systems, and we discuss why they are not always representative of the in vivo biofilms found in chronic infections. We present examples of methods that will help us to bridge the gap between in vitro and in vivo biofilm work, so that our bench-side data can ultimately be used to improve bedside treatment.

Drug Repurposing: A Strategy for Discovering Inhibitors against Emerging Viral Infections

2020 ◽  
Vol 27 ◽  
Author(s):  
Igor José dos Santos Nascimento ◽  
Thiago Mendonça de Aquino ◽  
Edeildo Ferreira da Silva-Júnior
Keyword(s):  
Viral Infections ◽  
Drug Repurposing ◽  
New Drugs ◽  
Exclusion Criterion ◽  
Viral Diseases ◽  
Time Interval ◽  
Research Groups ◽  
The World ◽  
Long Time ◽  
Emerging Viral Diseases

Background: Viral diseases are responsible for several deaths around the world. Over the past few years, the world has seen several outbreaks caused by viral diseases that for a long time seemed to possess no risk. These are diseases that have been forgotten for a long time and, until nowadays, there are no approved drugs or vaccines, leading the pharmaceutical industry and several research groups to run out of time in the search for new pharmacological treatments or prevention methods. In this context, drug repurposing proves to be a fast and economically viable technique, considering the fact that it uses drugs that have a well-established safety profile. Thus, in this review, we present the main advances in drug repurposing and their benefit for searching new treatments against emerging viral diseases. Methods: We conducted a search in the bibliographic databases (Science Direct, Bentham Science, PubMed, Springer, ACS Publisher, Wiley, and NIH’s COVID-19 Portfolio) using the keywords "drug repurposing", "emerging viral infections" and each of the diseases reported here (CoV; ZIKV; DENV; CHIKV; EBOV and MARV) as an inclusion/exclusion criterion. A subjective analysis was performed regarding the quality of the works for inclusion in this manuscript. Thus, the selected works were those that presented drugs repositioned against the emerging viral diseases presented here by means of computational, high-throughput screening or phenotype-based strategies, with no time limit and of relevant scientific value. Results: 291 papers were selected, 24 of which were CHIKV; 52 for ZIKV; 43 for DENV; 35 for EBOV; 10 for MARV; and 56 for CoV and the rest (72 papers) related to the drugs repurposing and emerging viral diseases. Among CoV-related articles, most were published in 2020 (31 papers), updating the current topic. Besides, between the years 2003 - 2005, 10 articles were created, and from 2011 - 2015 there were 7 articles, portraying the outbreaks that occurred at that time. For ZIKV, similar to CoV, most publications were during the period of outbreaks between the years 2016 - 2017 (23 articles). Similarly, most CHIKV (13 papers) and DENV (14 papers) publications occur at the same time interval. For EBOV (13 papers) and MARV (4 papers), they were between the years 2015 - 2016. Through this review, several drugs were highlighted that can be evolved in vivo and clinical trials as possible used against these pathogens showed that remdesivir represent potential treatments against CoV. Furthermore, ribavirin may also be a potential treatment against CHIKV; sofosbuvir against ZIKV; celgosivir against DENV, and favipiravir against EBOV and MARV, representing new hopes against these pathogens. Conclusions: The conclusions of this review manuscript show the potential of the drug repurposing strategy in the discovery of new pharmaceutical products, as from this approach, drugs that could be used against emerging viral diseases. Thus, this strategy deserves more attention among research groups and is a promising approach to the discovery of new drugs against emerging viral diseases and also other diseases.

scholarly journals COVID-19: Role of Nutrition and Supplementation

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 976
Author(s):  
Fiorenzo Moscatelli ◽  
Francesco Sessa ◽  
Anna Valenzano ◽  
Rita Polito ◽  
Vincenzo Monda ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Viral Infections ◽  
Overweight And Obesity ◽  
Shortness Of Breath ◽  
Nutritional Interventions ◽  
The World ◽  
Diet Regimen ◽  
Specific Diet

At the end of 2019, a new coronavirus (COVID-19) appeared on the world scene, which mainly affects the respiratory system, causing pneumonia and multi-organ failure, and, although it starts with common symptoms such as shortness of breath and fever, in about 2–3% of cases it leads to death. Unfortunately, to date, no specific treatments have been found for the cure of this virus and, therefore, it is advisable to implement all possible strategies in order to prevent infection. In this context, it is important to better define the role of all behaviors, in particular nutrition, in order to establish whether these can both prevent infection and improve the outcome of the disease in patients with COVID-19. In the literature, it is widely shown that states of malnutrition, overweight, and obesity negatively affect the immune system, leading to viral infections, and several studies have shown that nutritional interventions can act as immunostimulators, helping to prevent viral infections. Even if several measures, such as the assumption of a specific diet regimen, the use of dietary supplements, and other similar interventions, are promising for the prevention, management, and recovery of COVID-19 patients, it is important to highlight that strong data from randomized clinical trials are needed to support any such assumption. Considering this particular scenario, we present a literature review addressing several important aspects related to diet and SARS-CoV-2 infection, in order to highlight the importance of diet and supplementation in prevention and management of, as well as recovery from COVID-19.

scholarly journals N-Terminomics Strategies for Protease Substrates Profiling

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4699
Author(s):  
Mubashir Mintoo ◽  
Amritangshu Chakravarty ◽  
Ronak Tilvawala
Keyword(s):  
Mass Spectrometry ◽  
Protease Activity ◽  
Viral Infections ◽  
Mass Spectrometry Analysis ◽  
Post Translational Modification ◽  
Spectrometry Analysis ◽  
Physiological Conditions ◽  
Inflammatory Conditions ◽  
Biological Mixtures

Proteases play a central role in various biochemical pathways catalyzing and regulating key biological events. Proteases catalyze an irreversible post-translational modification called proteolysis by hydrolyzing peptide bonds in proteins. Given the destructive potential of proteolysis, protease activity is tightly regulated. Dysregulation of protease activity has been reported in numerous disease conditions, including cancers, neurodegenerative diseases, inflammatory conditions, cardiovascular diseases, and viral infections. The proteolytic profile of a cell, tissue, or organ is governed by protease activation, activity, and substrate specificity. Thus, identifying protease substrates and proteolytic events under physiological conditions can provide crucial information about how the change in protease regulation can alter the cellular proteolytic landscape. In recent years, mass spectrometry-based techniques called N-terminomics have become instrumental in identifying protease substrates from complex biological mixtures. N-terminomics employs the labeling and enrichment of native and neo-N-termini peptides, generated upon proteolysis followed by mass spectrometry analysis allowing protease substrate profiling directly from biological samples. In this review, we provide a brief overview of N-terminomics techniques, focusing on their strengths, weaknesses, limitations, and providing specific examples where they were successfully employed to identify protease substrates in vivo and under physiological conditions. In addition, we explore the current trends in the protease field and the potential for future developments.

scholarly journals Robots as intelligent assistants to face COVID-19 pandemic

2020 ◽  
Author(s):  
Valeria Seidita ◽  
Francesco Lanza ◽  
Arianna Pipitone ◽  
Antonio Chella
Keyword(s):  
Technological Progress ◽  
World Economy ◽  
The State ◽  
Research Groups ◽  
Negative Effects ◽  
The World ◽  
Intelligent Assistants

Abstract Motivation The epidemic at the beginning of this year, due to a new virus in the coronavirus family, is causing many deaths and is bringing the world economy to its knees. Moreover, situations of this kind are historically cyclical. The symptoms and treatment of infected patients are, for better or worse even for new viruses, always the same: more or less severe flu symptoms, isolation and full hygiene. By now man has learned how to manage epidemic situations, but deaths and negative effects continue to occur. What about technology? What effect has the actual technological progress we have achieved? In this review, we wonder about the role of robotics in the fight against COVID. It presents the analysis of scientific articles, industrial initiatives and project calls for applications from March to now highlighting how much robotics was ready to face this situation, what is expected from robots and what remains to do. Results The analysis was made by focusing on what research groups offer as a means of support for therapies and prevention actions. We then reported some remarks on what we think is the state of maturity of robotics in dealing with situations like COVID-19.

scholarly journals A Large-Scale COVID-19 Twitter Chatter Dataset for Open Scientific Research—An International Collaboration

Epidemiologia ◽  
2021 ◽  
Vol 2 (3) ◽  
pp. 315-324
Author(s):  
Juan M. Banda ◽  
Ramya Tekumalla ◽  
Guanyu Wang ◽  
Jingyuan Yu ◽  
Tuo Liu ◽  
...  
Keyword(s):  
Large Scale ◽  
Social Dynamics ◽  
Additional Data ◽  
Open Data ◽  
Data Sources ◽  
Research Projects ◽  
Research Groups ◽  
The World ◽  
Data Source

As the COVID-19 pandemic continues to spread worldwide, an unprecedented amount of open data is being generated for medical, genetics, and epidemiological research. The unparalleled rate at which many research groups around the world are releasing data and publications on the ongoing pandemic is allowing other scientists to learn from local experiences and data generated on the front lines of the COVID-19 pandemic. However, there is a need to integrate additional data sources that map and measure the role of social dynamics of such a unique worldwide event in biomedical, biological, and epidemiological analyses. For this purpose, we present a large-scale curated dataset of over 1.12 billion tweets, growing daily, related to COVID-19 chatter generated from 1 January 2020 to 27 June 2021 at the time of writing. This data source provides a freely available additional data source for researchers worldwide to conduct a wide and diverse number of research projects, such as epidemiological analyses, emotional and mental responses to social distancing measures, the identification of sources of misinformation, stratified measurement of sentiment towards the pandemic in near real time, among many others.

scholarly journals Antimalarial drugs—are they beneficial in rheumatic and viral diseases?—considerations in COVID-19 pandemic

2021 ◽  
Author(s):  
Bogna Grygiel-Górniak
Keyword(s):  
Connective Tissue ◽  
Viral Infections ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Antiviral Drugs ◽  
In Vivo Studies ◽  
Viral Diseases ◽  
Cardiac Complications

AbstractThe majority of the medical fraternity is continuously involved in finding new therapeutic schemes, including antimalarial medications (AMDs), which can be useful in combating the 2019-nCoV: coronavirus disease (COVID-19). For many decades, AMDs have been widely used in the treatment of malaria and various other anti-inflammatory diseases, particularly to treat autoimmune disorders of the connective tissue. The review comprises in vitro and in vivo studies, original studies, clinical trials, and consensus reports for the analysis, which were available in medical databases (e.g., PubMed). This manuscript summarizes the current knowledge about chloroquine (CQ)/hydroxychloroquine (HCQ) and shows the difference between their use, activity, recommendation, doses, and adverse effects on two groups of patients: those with rheumatic and viral diseases (including COVID-19). In the case of connective tissue disorders, AMDs are prescribed for a prolonged duration in small doses, and their effect is observed after few weeks, whereas in the case of viral infections, they are prescribed in larger doses for a short duration to achieve a quick saturation effect. In rheumatic diseases, AMDs are well tolerated, and their side effects are rare. However, in some viral diseases, the effect of AMDs is questionable or not so noticeable as suggested during the initial prognosis. They are mainly used as an additive therapy to antiviral drugs, but recent studies have shown that AMDs can diminish the efficacy of some antiviral drugs and may cause respiratory, kidney, liver, and cardiac complications.

scholarly journals Informed consent and informed intervention: SARS-CoV-2 vaccinations not just call for disclosure of newly emerging safety data but also for hypothesis generation and testing

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Johannes C. Fischer ◽  
Albrecht G. Schmidt ◽  
Edwin Bölke ◽  
Verena Keitel ◽  
Torsten Feldt ◽  
...  
Keyword(s):  
Health Care ◽  
Health Care Providers ◽  
Viral Infections ◽  
Safety Data ◽  
Hypothesis Generation ◽  
Care Providers ◽  
Vaccination Programs ◽  
Major Threat ◽  
The World ◽  
Population Scale

Abstract Background COVID-19 infection is a major threat to patients and health care providers around the world. One solution is the vaccination against SARS-CoV-2. Methods We performed a comprehensive query of the latest publications on the prevention of viral infections including the recent vaccination program and its side effects. Results The situation is evolving rapidly and there is no reasonable alternative to population-scale vaccination programs as currently enrolled. Conclusion Therefore, regulatory authorities should consider supplementing their conventional mandate of post-approval pharmacovigilance, which is based on the collection, assessment, and regulatory response to emerging safety findings.

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