10 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2020/06/25

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2020/06/24

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2020/06/24

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

9 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2020/06/23

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Fight against novel coronavirus: A perspective of medicinal chemists.

Eur J Med Chem. 2020 Jun 12;201:112559

Authors: Amin SA, Jha T

Abstract
The ongoing novel coronavirus disease (COVID-19) pandemic makes us painfully perceive that our bullet shells are blank so far for fighting against severe human coronavirus (HCoV). In spite of vast research work, it is crystal clear that the evident does not warrant the commercial blossoming of anti-HCoV drugs. In this circumstance, drug repurposing and/or screening of databases are the only fastest option. This study is an initiative to recapitulate the medicinal chemistry of severe acute respiratory syndrome (SARS)-CoV-2 (SARS-CoV-2). The aim is to present an exquisite delineation of the current research from the perspective of a medicinal chemist to allow the rapid development of anti-SARS-CoV-2 agents.

PMID: 32563814 [PubMed - as supplied by publisher]

7 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2020/06/21

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

11 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2020/06/20

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

10 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2020/06/20

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Network Medicine Framework for Identifying Drug Repurposing Opportunities for COVID-19.

ArXiv. 2020 Apr 15;:

Authors: Gysi DM, Do Valle Í, Zitnik M, Ameli A, Gan X, Varol O, Sanchez H, Baron RM, Ghiassian D, Loscalzo J, Barabási AL

Abstract
The COVID-19 pandemic demands the rapid identification of drug-repurpusing candidates. In the past decade, network medicine had developed a framework consisting of a series of quantitative approaches and predictive tools to study host-pathogen interactions, unveil the molecular mechanisms of the infection, identify comorbidities as well as rapidly detect drug repurpusing candidates. Here, we adapt the network-based toolset to COVID-19, recovering the primary pulmonary manifestations of the virus in the lung as well as observed comorbidities associated with cardiovascular diseases. We predict that the virus can manifest itself in other tissues, such as the reproductive system, and brain regions, moreover we predict neurological comorbidities. We build on these findings to deploy three network-based drug repurposing strategies, relying on network proximity, diffusion, and AI-based metrics, allowing to rank all approved drugs based on their likely efficacy for COVID-19 patients, aggregate all predictions, and, thereby to arrive at 81 promising repurposing candidates. We validate the accuracy of our predictions using drugs currently in clinical trials, and an expression-based validation of selected candidates suggests that these drugs, with known toxicities and side effects, could be moved to clinical trials rapidly.

PMID: 32550253 [PubMed]

Anticancer Activity of Pyrimethamine via Ubiquitin Mediated Degradation of AIMP2-DX2.

Molecules. 2020 Jun 15;25(12):

Authors: Kim DG, Park CM, Huddar S, Lim S, Kim S, Lee S

Abstract
While aminoacyl-tRNA synthetase-interacting multifunctional protein 2 (AIMP2) is a tumor suppressor, its exon 2-depleted splice variant (AIMP2-DX2 or shortly DX2) is highly expressed in human lung cancer, and the ratio of DX2 to AIMP2 increases according to the progression of lung cancer. In this study, pyrimethamine inhibited the level of DX2 (IC50 = 0.73 µM) in A549 cells expressing nanoluciferase-tagged DX2. In a panel of 5 lung cancer cell lines with various DX2 levels, pyrimethamine most potently suppressed the growth of H460 cells, which express high levels of DX2 (GI50 = 0.01 µM). An immunoblot assay in H460 cells showed that pyrimethamine decreased the DX2 level dose-dependently but did not affect the AIMP2 level. Further experiments confirmed that pyrimethamine resulted in ubiquitination-mediated DX2 degradation. In an in vivo mouse xenograft assay using H460 cells, intraperitoneal administration of pyrimethamine significantly reduced the tumor size and weight, comparable with the effects of taxol, without affecting body weight. Analysis of tumor tissue showed a considerably high concentration of pyrimethamine with a decreased levels of DX2. These results suggest that pyrimethamine, currently used as anti-parasite drug, could be repurposed to treat lung cancer patients expressing high level of DX2.

PMID: 32549310 [PubMed - in process]

Sitagliptin Repositioning in SARS-CoV-2: Effects on ACE-2, CD-26, and Inflammatory Cytokine Storms in the Lung.

Iran J Allergy Asthma Immunol. 2020 May 17;19(S1):10-12

Authors: Dastan F, Abedini A, Shahabi S, Kiani A, Saffaei A, Zare A

Abstract
No Abstract.

PMID: 32534505 [PubMed - indexed for MEDLINE]

Drug researchers pursue new lines of attack against COVID-19.

Nat Biotechnol. 2020 06;38(6):659-662

Authors: Harrison C

PMID: 32417850 [PubMed - indexed for MEDLINE]

Harnessing CAR T-cell Insights to Develop Treatments for Hyperinflammatory Responses in Patients with COVID-19.

Cancer Discov. 2020 06;10(6):775-778

Authors: Agarwal S, June CH

Abstract
Cytokine release and macrophage activation contribute to immunopathology after SARS-CoV-2 infection. We discuss approaches to decrease the morbidity and mortality in patients with COVID-19 by repurposing existing drugs previously developed for cancer therapy.

PMID: 32303509 [PubMed - indexed for MEDLINE]

7 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2020/06/18

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2020/06/17

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Virtual screening, ADME/Tox predictions and the drug repurposing concept for future use of old drugs against the COVID-19.

Life Sci. 2020 Jun 11;:117963

Authors: da Silva Hage-Melim LI, Federico LB, de Oliveira NKS, Francisco VCC, Correa LC, de Lima HB, Gomes SQ, Barcelos MP, Francischini IAG, de Paula da Silva CHT

Abstract
The new Coronavirus (SARS-CoV-2) is the cause of a serious infection in the respiratory tract called COVID-19. Structures of the main protease of SARS-CoV-2 (Mpro), responsible for the replication of the virus, have been solved and quickly made available, thus allowing the design of compounds that could interact with this protease and thus to prevent the progression of the disease by avoiding the viral peptide to be cleaved, so that smaller viral proteins can be released into the host's plasma. These structural data are extremely important for in silico design and development of compounds as well, being possible to quick and effectively identify potential inhibitors addressed to such enzyme's structure. Therefore, in order to identify potential inhibitors for Mpro, we used virtual screening approaches based with the structure of the enzyme and two compounds libraries, targeted to SARS-CoV-2, containing compounds with predicted activity against Mpro. In this way, we selected, through docking studies, the 100 top-ranked compounds, which followed for subsequent studies of pharmacokinetic and toxicity predictions. After all the simulations and predictions here performed, we obtained 10 top-ranked compounds that were again in silico analyzed inside the Mpro catalytic site, together some drugs that are being currently investigated for treatment of COVID-19. After proposing and analyzing the interaction modes of these compounds, we submitted one molecule then selected as template to a 2D similarity study in a database containing drugs approved by FDA and we have found and indicated Apixaban as a potential drug for future treatment of COVID-19.

PMID: 32535080 [PubMed - as supplied by publisher]

Diacerein: A potential multi-target therapeutic drug for COVID-19.

Med Hypotheses. 2020 Jun 01;144:109920

Authors: de Oliveira PG, Termini L, Durigon EL, Lepique AP, Sposito AC, Boccardo E

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 19 (COVID-19), was declared pandemic by the World Health Organization in March 2020. SARS-CoV-2 binds its host cell receptor, angiotensin-converting enzyme 2 (ACE2), through the viral spike (S) protein. The mortality related to severe acute respiratory distress syndrome (ARDS) and multi-organ failure in COVID-19 patients has been suggested to be connected with cytokine storm syndrome (CSS), an excessive immune response that severely damages healthy lung tissue. In addition, cardiac symptoms, including fulminant myocarditis, are frequent in patients in a severe state of illness. Diacerein (DAR) is an anthraquinone derivative drug whose active metabolite is rhein. Different studies have shown that this compound inhibits the IL-1, IL-2, IL-6, IL-8, IL-12, IL-18, TNF-α, NF-κB and NALP3 inflammasome pathways. The antiviral activity of rhein has also been documented. This metabolite prevents hepatitis B virus (HBV) replication and influenza A virus (IAV) adsorption and replication through mechanisms involving regulation of oxidative stress and alterations of the TLR4, Akt, MAPK, and NF-κB signalling pathways. Importantly, rhein inhibits the interaction between the SARS-CoV S protein and ACE2 in a dose-dependent manner, suggesting rhein as a potential therapeutic agent for the treatment of SARS-CoV infection. Based on these findings, we hypothesize that DAR is a multi-target drug useful for COVID-19 treatment. This anthraquinone may control hyperinflammatory conditions by multi-faceted cytokine inhibition and by reducing viral infection.

PMID: 32534337 [PubMed - as supplied by publisher]

Individualizing risk prediction for positive COVID-19 testing: results from 11,672 patients.

Chest. 2020 Jun 10;:

Authors: Jehi L, Ji X, Milinovich A, Erzurum S, Rubin B, Gordon S, Young J, Kattan MW

Abstract
BACKGROUND: Coronavirus disease-2019 (COVID-19) is sweeping the globe. Despite multiple case-series, actionable knowledge to proactively tailor decision-making is missing.
RESEARCH QUESTION: Can a statistical model accurately predict infection with COVID?
STUDY DESIGN: and Methods: We developed a prospective registry of all patients tested for COVID-19 in Cleveland Clinic to create individualized risk prediction models. We focus here on likelihood of a positive nasal or oropharyngeal COVID-19 test [COVID-19 (+)]. A least absolute shrinkage and selection operator (LASSO) logistic regression algorithm was constructed, which removed variables that were not contributing to the model's cross-validated concordance index. Following external validation in a temporally and geographically-distinct cohort, the statistical prediction model was illustrated as a nomogram and deployed in an online risk calculator.
RESULTS: 11,672 patients fulfilled study criteria in the development cohort, including 818 (7.0%) COVID-19 (+), and 2,295 patients fulfilled criteria in the validation cohort including 290 COVID-19 (+). Males, African Americans, older patients, and those with known COVID-19 exposure were at higher risk of being COVID-19 (+). Risk was reduced in those who had pneumococcal polysaccharide or influenza vaccine, or were on melatonin, paroxetine, or carvedilol. Our model had favorable discrimination (c-statistic=0.863 in development; 0.840 in validation cohort) and calibration. We present sensitivity, specificity, negative predictive value, and positive predictive value at different prediction cut-offs.The calculator is freely available at https://riskcalc.org/COVID19.
INTERPRETATION: Prediction of a COVID-19 (+) test is possible and could help direct healthcare resources. We demonstrate relevance of age, race, gender, and socioeconomic characteristics in COVID-19-susceptibility and suggest a potential modifying role of certain common vaccinations and drugs identified in drug-repurposing studies.

PMID: 32533957 [PubMed - as supplied by publisher]

[Update on beta blockers in 2020].

Rev Med Interne. 2020 Jun 09;:

Authors: Bejan-Angoulvant T, Angoulvant D

Abstract
Beta-blockers (BB) are an heterogenous set of molecules actively blocking β adrenergic receptors. Their pharmacological properties depend on their various effects on the adrenergic signalling. Although they are no longer a first-choice treatment in hypertensive patients, they remain a cornerstone of pharmacological strategy in several cardiovascular diseases such as stable angina, heart failure, arrythmia and aortic related connective diseases. Beyond their usual non cardiovascular indications such as migraine, hepatic cirrhosis, glaucoma, infantile hemangioma, and hyperthyroidism, new therapeutic fields are under scrutiny. Potential BB therapeutic repurposing is being investigated in COPD and cancer patients. This narrative review first encompasses the basic pharmacological knowledge that may be useful for the clinician. Then it will detail BB main indications before exploring new therapeutic fields.

PMID: 32532560 [PubMed - as supplied by publisher]

Repurposing the Dihydropyridine Calcium Channel Inhibitor Nicardipine as a Nav1.8 Inhibitor In Vivo for Pitt Hopkins Syndrome.

Pharm Res. 2020 Jun 11;37(7):127

Authors: Ekins S, Puhl AC, Davidow A

Abstract
PURPOSE: Individuals with the rare genetic disorder Pitt Hopkins Syndrome (PTHS) do not have sufficient expression of the transcription factor 4 (TCF4) which is located on chromosome 18. TCF4 is a basic helix-loop-helix E protein that is critical for the normal development of the nervous system and the brain in humans. PTHS patients lacking sufficient TCF4 frequently display gastrointestinal issues, intellectual disability and breathing problems. PTHS patients also commonly do not speak and display distinctive facial features and seizures. Recent research has proposed that decreased TCF4 expression can lead to the increased translation of the sodium channel Nav1.8. This in turn results in increased after-hyperpolarization as well as altered firing properties. We have recently identified through a drug repurposing screen an FDA approved dihydropyridine calcium antagonist nicardipine used to treat angina, which inhibited Nav1.8.
METHODS: We have now performed behavioral testing in groups of 10 male Tcf4(± ) PTHS mice dosing by oral gavage at 3 mg/kg once a day for 3 weeks using standard methods to assess sociability, nesting, fear conditioning, self-grooming, open field and test of force.
RESULTS: Nicardipine returned this spectrum of behavioral deficits in the Tcf4(± ) PTHS mouse model to WT levels and resulted in statistically significant results.
CONCLUSIONS: These in vivo results in the well characterized Tcf4(± ) PTHS mice may suggest the potential to test this already approved drug further in a clinical study with PTHS patients or suggest the potential for use off label under compassionate use with their physician.

PMID: 32529312 [PubMed - in process]