scholarly journals Characterization of highly conserved G-quadruplex motifs as potential drug targets in Streptococcus pneumoniae

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Subodh Kumar Mishra ◽  
Neha Jain ◽  
Uma Shankar ◽  
Arpita Tawani ◽  
Tarun Kumar Sharma ◽  
...  
2019 ◽  
Vol 16 ◽  
pp. 698-706 ◽  
Author(s):  
Subodh Kumar Mishra ◽  
Uma Shankar ◽  
Neha Jain ◽  
Kriti Sikri ◽  
Jaya Sivaswami Tyagi ◽  
...  

2013 ◽  
Vol 89 ◽  
pp. 202-214 ◽  
Author(s):  
Gagan Garg ◽  
Dolores Bernal ◽  
Maria Trelis ◽  
Javier Forment ◽  
Javier Ortiz ◽  
...  

2013 ◽  
Vol 57 (12) ◽  
pp. 5969-5976 ◽  
Author(s):  
Peter D. Ziniel ◽  
Janish Desai ◽  
Cynthia L. Cass ◽  
Craig Gatto ◽  
Eric Oldfield ◽  
...  

ABSTRACTSchistosomiasis affects over 200 million people worldwide, with over 200,000 deaths annually. Currently, praziquantel is the only drug available against schistosomiasis. We report here thatSchistosoma mansonifarnesyl diphosphate synthase (SmFPPS) and geranylgeranyl diphosphate synthase (SmGGPPS) are potential drug targets for the treatment of schistosomiasis. We expressed active, recombinantSmFPPS andSmGGPPS for subsequent kinetic characterization and testing against a variety of bisphosphonate inhibitors. RecombinantSmFPPS was found to be a soluble 44.2-kDa protein, whileSmGGPPS was a soluble 38.3-kDa protein. Characterization of the substrate utilization of the two enzymes indicates that they have overlapping substrate specificities. AgainstSmFPPS, several bisphosphonates had 50% inhibitory concentrations (IC50s) in the low micromolar to nanomolar range; these inhibitors had significantly less activity againstSmGGPPS. Several lipophilic bisphosphonates were active againstex vivoadult worms, with worm death occurring over 4 to 6 days. These results indicate that FPPS and GGPPS could be of interest in the context of the emerging resistance to praziquantel in schistosomiasis therapy.


mSystems ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Arijit Bhattacharya ◽  
Mansi Sharma ◽  
Charles Packianathan ◽  
Barry P. Rosen ◽  
Philippe Leprohon ◽  
...  

The two main cellular metabolic one-carbon donors are reduced folates and S-adenosylmethionine, whose biosynthetic pathways have proven highly effective in chemotherapeutic interventions in various cell types. Sinefungin, a nucleoside analogue of S-adenosylmethionine, was shown to have potent activity against the protozoan parasite Leishmania. Here, we studied resistance to sinefungin using whole-genome approaches as a way to further our understanding of the role of S-adenosylmethionine in this parasite and to reveal novel potential drug targets. These approaches allowed the characterization of novel features related to S-adenosylmethionine function in Leishmania which could further help in the development of sinefungin-like compounds against this pathogenic parasite.


Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1784
Author(s):  
Antonio Real-Hohn ◽  
Dieter Blaas

Rhinoviruses (RVs) are the main cause of recurrent infections with rather mild symptoms characteristic of the common cold. Nevertheless, RVs give rise to enormous numbers of absences from work and school and may become life-threatening in particular settings. Vaccination is jeopardised by the large number of serotypes eliciting only poorly cross-neutralising antibodies. Conversely, antivirals developed over the years failed FDA approval because of a low efficacy and/or side effects. RV species A, B, and C are now included in the fifteen species of the genus Enteroviruses based upon the high similarity of their genome sequences. As a result of their comparably low pathogenicity, RVs have become a handy model for other, more dangerous members of this genus, e.g., poliovirus and enterovirus 71. We provide a short overview of viral proteins that are considered potential drug targets and their corresponding drug candidates. We briefly mention more recently identified cellular enzymes whose inhibition impacts on RVs and comment novel approaches to interfere with infection via aggregation, virus trapping, or preventing viral access to the cell receptor. Finally, we devote a large part of this article to adding the viral RNA genome to the list of potential drug targets by dwelling on its structure, folding, and the still debated way of its exit from the capsid. Finally, we discuss the recent finding that G-quadruplex stabilising compounds impact on RNA egress possibly via obfuscating the unravelling of stable secondary structural elements.


2014 ◽  
Vol 2014 ◽  
pp. 1-6
Author(s):  
Mahantesh M. Kurjogi ◽  
Basappa B. Kaliwal

The purpose of this study is to deal with aetiology causing bovine mastitis; bovine herpes virus is also responsible for causing bovine mastitis but studies on viruses have been neglected as historical mastitis research has concentrated only on bacterial pathogens. Therefore, present study aims to make an in silico identification and characterization of potential drug targets in bovine herpes virus 4 by computational methods using various bioinformatics tools. In the current investigation 5 proteins of BoHV 4 were found to be nonhomologous to the host Bos taurus; these nonhomology proteins were believed to be inevitable proteins of BoHV 4 as they were specific to the virus; however 378 proteins were homologous to the host protein. The in silico physicochemical characterization of 5 proteins of BoHV 4 indicated that all the proteins of the virus were having more or less similar characteristics. Perhaps the knowledge of the present study may help in drug discovery which have high affinity to target site. Possible drug discovery to manage bovine mastitis with a help of bioinformatics tool is more significant and, specific and, reduces time and complications involved in clinical trials.


Sign in / Sign up

Export Citation Format

Share Document