Hydrogel based lipid-oligonucleotides: a new route to self-delivery of therapeutic sequences

2021 ◽  
Author(s):  
Sébastien Benizri ◽  
Alexandra Gaubert ◽  
Charlotte Soulard ◽  
Etienne Gontier ◽  
Isabelle Svhan ◽  
...  

Synthetic OligoNucleotides (ON) provide promising therapeutic tools for controlling specifically genetic expression in a broad range of diseases from cancers to viral infections. Beside their chemical stability and intracellular delivery,...

2021 ◽  
Vol 29 ◽  
Author(s):  
Yves Blériot ◽  
Nicolas Auberger ◽  
Jérôme Désiré

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.


2021 ◽  
Vol 8 (1) ◽  
pp. 373-391
Author(s):  
Khyati Girdhar ◽  
Amaya Powis ◽  
Amol Raisingani ◽  
Martina Chrudinová ◽  
Ruixu Huang ◽  
...  

Over the past decades, there have been tremendous efforts to understand the cross-talk between viruses and host metabolism. Several studies have elucidated the mechanisms through which viral infections manipulate metabolic pathways including glucose, fatty acid, protein, and nucleotide metabolism. These pathways are evolutionarily conserved across the tree of life and extremely important for the host's nutrient utilization and energy production. In this review, we focus on host glucose, glutamine, and fatty acid metabolism and highlight the pathways manipulated by the different classes of viruses to increase their replication. We also explore a new system of viral hormones in which viruses mimic host hormones to manipulate the host endocrine system. We discuss viral insulin/IGF-1-like peptides and their potential effects on host metabolism. Together, these pathogenesis mechanisms targeting cellular signaling pathways create a multidimensional network of interactions between host and viral proteins. Defining and better understanding these mechanisms will help us to develop new therapeutic tools to prevent and treat viral infections.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Flávia M. Zimbres ◽  
Attila Tárnok ◽  
Henning Ulrich ◽  
Carsten Wrenger

Worldwide the entire human population is at risk of infectious diseases of which a high degree is caused by pathogenic protozoans, worms, bacteria, and virus infections. Moreover the current medications against pathogenic agents are losing their efficacy due to increasing and even further spreading drug resistance. Therefore, there is an urgent need to discover novel diagnostic as well as therapeutic tools against infectious agents. In view of that, the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) represents a powerful technology to target selectively pathogenic factors as well as entire bacteria or viruses. SELEX uses a large combinatorial oligonucleic acid library (DNA or RNA) which is processed a by high-fluxin vitroscreen of iterative cycles. The selected ligands, termed aptamers, are characterized by high specificity and affinity to their target molecule, which are already exploited in diagnostic and therapeutic applications. In this minireview we will discuss the current status of the SELEX technique applied on bacterial and viral pathogens.


Viruses ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 704 ◽  
Author(s):  
Aslaa Ahmed ◽  
Gavriella Siman-Tov ◽  
Grant Hall ◽  
Nishank Bhalla ◽  
Aarthi Narayanan

Successful in vivo infection following pathogen entry requires the evasion and subversion of multiple immunological barriers. Antimicrobial peptides (AMPs) are one of the first immune pathways upregulated during infection by multiple pathogens, in multiple organs in vivo. In humans, there are many classes of AMPs exhibiting broad antimicrobial activities, with defensins and the human cathelicidin LL-37 being the best studied examples. Whereas historically the efficacy and therapeutic potential of AMPs against bacterial infection has been the primary focus of research, recent studies have begun to elucidate the antiviral properties of AMPs as well as their role in regulation of inflammation and chemoattraction. AMPs as therapeutic tools seem especially promising against emerging infectious viral pathogens for which no approved vaccines or treatments are currently available, such as dengue virus (DENV) and Zika virus (ZIKV). In this review, we summarize recent studies elucidating the efficacy and diverse mechanisms of action of various classes of AMPs against multiple viral pathogens, as well as the potential use of human AMPs in novel antiviral therapeutic strategies.


Author(s):  
Homa Boroumand ◽  
Fereshteh Badie ◽  
Samaneh Mazaheri ◽  
Zeynab Sadat Seyedi ◽  
Javid Sadri Nahand ◽  
...  

Viral infections, in addition to damaging host cells, can compromise the host immune system, leading to frequent relapse or long-term persistence. Viruses have the capacity to destroy the host cell while liberating their own RNA or DNA in order to replicate within additional host cells. The viral life cycle makes it challenging to develop anti-viral drugs. Nanotechnology-based approaches have been suggested to deal effectively with viral diseases, and overcome some limitations of anti-viral drugs. Nanotechnology has enabled scientists to overcome the challenges of solubility and toxicity of anti-viral drugs, and can enhance their selectivity towards viruses and virally infected cells, while preserving healthy host cells. Chitosan is a naturally occurring polymer that has been used to construct nanoparticles (NPs), which are biocompatible, biodegradable, less toxic, easy to prepare, and can function as effective drug delivery systems (DDSs). Furthermore, chitosan is Generally Recognized as Safe (GRAS) by the US Food and Drug Administration (U.S. FDA). Chitosan NPs have been used in drug delivery by the oral, ocular, pulmonary, nasal, mucosal, buccal, or vaginal routes. They have also been studied for gene delivery, vaccine delivery, and advanced cancer therapy. Multiple lines of evidence suggest that chitosan NPs could be used as new therapeutic tools against viral infections. In this review we summarize reports concerning the therapeutic potential of chitosan NPs against various viral infections.


2003 ◽  
Vol 3 (1) ◽  
pp. 237-238
Author(s):  
T. Kubo ◽  
Y. Anno ◽  
M. Yano ◽  
K. Takamori ◽  
B. Rumiana ◽  
...  

Author(s):  
William B. McCombs ◽  
Cameron E. McCoy

Recent years have brought a reversal in the attitude of the medical profession toward the diagnosis of viral infections. Identification of bacterial pathogens was formerly thought to be faster than identification of viral pathogens. Viral identification was dismissed as being of academic interest or for confirming the presence of an epidemic, because the patient would recover or die before this could be accomplished. In the past 10 years, the goal of virologists has been to present the clinician with a viral identification in a matter of hours. This fast diagnosis has the potential for shortening the patient's hospital stay and preventing the administering of toxic and/or expensive antibiotics of no benefit to the patient.


Author(s):  
J. R. Hully ◽  
K. R. Luehrsen ◽  
K. Aoyagi ◽  
C. Shoemaker ◽  
R. Abramson

The development of PCR technology has greatly accelerated medical research at the genetic and molecular levels. Until recently, the inherent sensitivity of this technique has been limited to isolated preparations of nucleic acids which lack or at best have limited morphological information. With the obvious exception of cell lines, traditional PCR or reverse transcription-PCR (RT-PCR) cannot identify the cellular source of the amplified product. In contrast, in situ hybridization (ISH) by definition, defines the anatomical location of a gene and/or it’s product. However, this technique lacks the sensitivity of PCR and cannot routinely detect less than 10 to 20 copies per cell. Consequently, the localization of rare transcripts, latent viral infections, foreign or altered genes cannot be identified by this technique. In situ PCR or in situ RT-PCR is a combination of the two techniques, exploiting the sensitivity of PCR and the anatomical definition provided by ISH. Since it’s initial description considerable advances have been made in the application of in situ PCR, improvements in protocols, and the development of hardware dedicated to in situ PCR using conventional microscope slides. Our understanding of the importance of viral latency or viral burden in regards to HIV, HPV, and KSHV infections has benefited from this technique, enabling detection of single viral copies in cells or tissue otherwise thought to be normal. Clearly, this technique will be useful tool in pathobiology especially carcinogenesis, gene therapy and manipulations, the study of rare gene transcripts, and forensics.


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