scholarly journals In silico Repositioning of Approved Drugs Against Schistosoma mansoni Energy Metabolism Targets

2018 ◽  
Author(s):  
Nicole Melo Calixto ◽  
Daniela Braz dos Santos ◽  
José Clecildo Barreto Bezerra ◽  
Lourival de Almeida Silva
Keyword(s):  
Energy Metabolism ◽  
Schistosoma Mansoni ◽  
In Silico ◽  
New Drugs ◽  
Effective Alternative ◽  
Metabolism Enzymes ◽  
Low Efficiency ◽  
Approved Drugs ◽  
Expensive Process ◽  
Analyze Data

AbstractSchistosomiasis is a neglected parasitosis caused by Schistosoma spp. Praziquantel is used for the chemoprophylaxis and treatment of this disease. Although this monotherapy is effective, the risk of resistance and its low efficiency against immature worms compromises its effectiveness. Therefore, it is necessary to develop new schistosomicide drugs. However, the development of new drugs is a long and expensive process. The repositioning of approved drugs has been proposed as a quick, cheap, and effective alternative to solve this problem. This study employs chemogenomic analysis with use of bioinformatics tools to search, identify, and analyze data on approved drugs with the potential to inhibit Schistosoma mansoni energy metabolism enzymes. The TDR Targets Database, Gene DB, Protein, DrugBank, Therapeutic Targets Database (TTD), Promiscuous, and PubMed databases were used. Fifty-nine target proteins were identified, of which 18 had one or more approved drugs. The results identified 20 potential drugs for schistosomiasis treatment, all approved for use in humans.

scholarly journals In silico repositioning of approved drugs against Schistosoma mansoni energy metabolism targets

PLoS ONE ◽  
2018 ◽  
Vol 13 (12) ◽  
pp. e0203340 ◽  
Author(s):  
Nicole Melo Calixto ◽  
Daniela Braz dos Santos ◽  
José Clecildo Barreto Bezerra ◽  
Lourival de Almeida Silva
Keyword(s):  
Energy Metabolism ◽  
Schistosoma Mansoni ◽  
In Silico ◽  
Approved Drugs

scholarly journals In SilicoSearch of Energy Metabolism Inhibitors for Alternative Leishmaniasis Treatments

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Lourival A. Silva ◽  
Marina C. Vinaud ◽  
Ana Maria Castro ◽  
Pedro Vítor L. Cravo ◽  
José Clecildo B. Bezerra
Keyword(s):  
Developing Countries ◽  
Energy Metabolism ◽  
Complex Disease ◽  
Current Treatment ◽  
New Drugs ◽  
Socioeconomic Impact ◽  
Search Criterion ◽  
Metabolism Enzymes ◽  
Target Database ◽  
Specific Inhibitors

Leishmaniasis is a complex disease that affects mammals and is caused by approximately 20 distinct protozoa from the genusLeishmania. Leishmaniasis is an endemic disease that exerts a large socioeconomic impact on poor and developing countries. The current treatment for leishmaniasis is complex, expensive, and poorly efficacious. Thus, there is an urgent need to develop more selective, less expensive new drugs. The energy metabolism pathways ofLeishmaniainclude several interesting targets for specific inhibitors. In the present study, we sought to establish which energy metabolism enzymes inLeishmaniacould be targets for inhibitors that have already been approved for the treatment of other diseases. We were able to identify 94 genes and 93Leishmaniaenergy metabolism targets. Using each gene’s designation as a search criterion in the TriTrypDB database, we located the predicted peptide sequences, which in turn were used to interrogate the DrugBank, Therapeutic Target Database (TTD), and PubChem databases. We identified 44 putative targets of which 11 are predicted to be amenable to inhibition by drugs which have already been approved for use in humans for 11 of these targets. We propose that these drugs should be experimentally tested and potentially used in the treatment of leishmaniasis.

scholarly journals In silico REPOSITIONING OF NEW DRUGS AGAINST Schistosoma mansoni

2018 ◽  
Vol 47 (3) ◽  
pp. 159
Author(s):  
Jose Clecildo Barreto Bezerra ◽  
Morgana Elias Arantes ◽  
Carolina Horta Andrade ◽  
Lourival Almeida Silva ◽  
Bruno Junior Neves
Keyword(s):  
Schistosoma Mansoni ◽  
In Silico ◽  
New Drugs

scholarly journals A Protocol for Identifying Potentially Repurposable Drugs Using Online Tools and Databases

2016 ◽  
Author(s):  
Aditi Chattopadhyay ◽  
Madhavi Ganapathiraju
Keyword(s):  
In Silico ◽  
Small Cell Lung Carcinoma ◽  
Drug Repurposing ◽  
Cost Effective ◽  
Age Related Macular Degeneration ◽  
New Drugs ◽  
Compound Identification ◽  
Cell Lung Carcinoma ◽  
Age Related ◽  
Approved Drugs

Traditional methods for discovery and development of new drugs can be a very time-consuming and expensive process because it includes several stages such as compound identification, pre-clinical and clinical trials before the drug is approved by the US Food and Drug Administration (FDA). Therefore, drug repurposing, namely using currently FDA-approved drugs as therapeutics for other diseases than what they are originally prescribed for, is emerging to be a faster and more cost-effective alternative to current drug discovery methods. In this paper, we have described a three-step in silico protocol for analyzing transcriptomics data using online databases and bioinformatics tools for identifying potentially repurposable drugs. The efficacy of this protocol was evaluated by comparing its predictions with the findings of two case studies of recently reported repurposed drugs: HIV treating drug Zidovudine for the treatment of Dry Age-Related Macular Degeneration and the antidepressant Imipramine for Small-Cell Lung Carcinoma. The proposed protocol successfully identified the published findings, thus demonstrating the efficacy of this method. In addition, it also yielded several novel predictions that have not yet been published, including the finding that Imipramine could potentially treat Severe Acute Respiratory Syndrome (SARS), a disease that currently does not have any treatment or vaccine. Since this in-silico protocol is simple to use and does not require advanced computer skills, we believe any motivated participant with access to these databases and tools would be able to apply it to large datasets to identify other potentially repurposable drugs in the future.

scholarly journals In Silico Repositioning-Chemogenomics Strategy Identifies New Drugs with Potential Activity against Multiple Life Stages of Schistosoma mansoni

2015 ◽  
Vol 9 (1) ◽  
pp. e3435 ◽  
Author(s):  
Bruno J. Neves ◽  
Rodolpho C. Braga ◽  
José C. B. Bezerra ◽  
Pedro V. L. Cravo ◽  
Carolina H. Andrade
Keyword(s):  
Schistosoma Mansoni ◽  
In Silico ◽  
New Drugs ◽  
Life Stages ◽  
Potential Activity

scholarly journals REPURPOSING FDA-APPROVED DRUGS AGAINST MULTIPLE PROTEINS OF SARS-CoV-2: AN in silico STUDY

2021 ◽  
pp. e00845
Author(s):  
Alfred Olaoluwa Akinlalu ◽  
Annapoorna Chamundi ◽  
Donald Terseer Yakumbur ◽  
Funmilayo I. Deborah Afolayan ◽  
Ijeoma Akunna Duru ◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Study ◽  
Approved Drugs ◽  
Fda Approved Drugs

Safety-Related Postmarketing Modifications of Drugs for Hematological Malignancies

2019 ◽  
Vol 143 (1) ◽  
pp. 73-77
Author(s):  
Anat Gafter-Gvili ◽  
Ariadna Tibau ◽  
Pia Raanani ◽  
Daniel Shepshelovich
Keyword(s):  
Hematological Malignancies ◽  
New Drugs ◽  
Priority Review ◽  
Regulatory Review ◽  
Regulatory Pathways ◽  
The Us ◽  
Black Box Warnings ◽  
Accelerated Approval ◽  
Drug Approvals ◽  
Approved Drugs

The prevalence of safety-related postmarketing label modifications of medications for hematological malignancies is unknown. We identified 35 new drugs indicated for hematological malignancies approved by the US Food and Drug Administration between January 1999 and December 2014. Characteristics of supporting trials and safety-related label modifications from approval to December 2017 were collected from drug labels. Regulatory review and approval pathways were also collected. New drug approvals were supported by trials with a median of 167 patients (interquartile range 115–316). All drugs were approved based on surrogate endpoints. Twenty-seven drug approvals (77%) were not supported by randomized controlled trials. All drugs received orphan drug designation, and most were granted fast track designation, priority review, and accelerated approval (83, 74, and 60%, respectively). A total of 28 drugs (80%) had postmarketing safety-related label modifications. Additions to black box warnings, contraindications, warnings and precautions, and common adverse reactions were identified in 31, 11, 77, and 46% of drugs, respectively. Five drugs (14%) were permanently or temporarily withdrawn from the US market. Drugs for hematological malignancies are often approved based on limited evidence through expedited regulatory pathways with incomplete safety profiles. Hematologists should be vigilant for unrecognized side effects when prescribing newly approved drugs.

In Silico Modeling of FDA-Approved Drugs for Discovery of Therapies Against Neglected Diseases: A Drug Repurposing Approach

2019 ◽  
pp. 625-648 ◽  
Author(s):  
Carolina L. Belllera ◽  
María L. Sbaraglini ◽  
Lucas N. Alberca ◽  
Juan I. Alice ◽  
Alan Talevi
Keyword(s):  
In Silico ◽  
Drug Repurposing ◽  
Neglected Diseases ◽  
In Silico Modeling ◽  
Approved Drugs ◽  
Fda Approved Drugs

scholarly journals Praziquantel in a Clay Nanoformulation Shows More Bioavailability and Higher Efficacy against Murine Schistosoma mansoni Infection

2015 ◽  
Vol 59 (6) ◽  
pp. 3501-3508 ◽  
Author(s):  
Gina S. El-Feky ◽  
Wael S. Mohamed ◽  
Hanaa E. Nasr ◽  
Naglaa M. El-Lakkany ◽  
Sayed H. Seif el-Din ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Rate Constant ◽  
Elimination Rate ◽  
New Drugs ◽  
Egg Load ◽  
Potential Cost ◽  
Time Curve ◽  
Content Type ◽  
Mmt Clay

ABSTRACTConsideration of existing compounds always simplifies and shortens the long and difficult process of discovering new drugs specifically for diseases of developing countries, an approach that may add to the significant potential cost savings. This study focused on improving the biological characteristics of the already-existing antischistosomal praziquantel (PZQ) by incorporating it into montmorillonite (MMT) clay as a delivery carrier to overcome its known bioavailability drawbacks. The oral bioavailability of a PZQ-MMT clay nanoformulation and itsin vivoefficacy againstSchistosoma mansoniwere investigated. The PZQ-MMT clay nanoformulation provided a preparation with a controlled release rate, a decrease in crystallinity, and an appreciable reduction in particle size. Uninfected and infected mice treated with PZQ-MMT clay showed 3.61- and 1.96-fold and 2.16- and 1.94-fold increases, respectively, in area under the concentration-time curve from 0 to 8 h (AUC0–8) and maximum concentration of drug in serum (Cmax), with a decrease in elimination rate constant (kel) by 2.84- and 1.35-fold and increases in the absorption rate constant (ka) and half-life (t1/2e) by 2.11- and 1.51-fold and 2.86- and 1.34-fold, respectively, versus the corresponding conventional PZQ-treated groups. This improved bioavailability has been expressed in higher efficacy of the drug, where the dose necessary to kill 50% of the worms was reduced by >3-fold (PZQ 50% effective dose [ED50] was 20.25 mg/kg of body weight for PZQ-MMT clay compared to 74.07 mg/kg for conventional PZQ), with significant reduction in total tissue egg load and increase in total immature, mature, and dead eggs in most of the drug-treated groups. This formulation showed better bioavailability, enhanced antischistosomal efficacy, and a safer profile despite the longer period of residence in the systemic circulation. Although the conventional drug's toxicity was not examined, animal mortality rates were not different between groups receiving the test PZQ-clay nanoformulation and conventional PZQ.

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