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 2020/08/14

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.

Anti-inflammatory and antiviral roles of hydrogen sulfide: rationale for considering H2 S-donors in COVID-19 therapy.

Br J Pharmacol. 2020 Aug 11;:

Authors: Citi V, Martelli A, Brancaleone V, Brogi S, Gojon G, Montanaro R, Morales G, Testai L, Calderone V

Abstract
The COVID-19 pandemic caused by new betacoronavirus SARS-Cov-2 demands rapid exploration of safe and effective therapeutic options. In this perspective, "drug repurposing" aims to represent a rapid and valuable strategy. In the last decades, the endogenous gasotransmitter hydrogen sulfide (H2 S) has emerged as a ubiquitous modulator of several biological functions. Early studies pointed out its importance in the regulation of numerous biological functions and systems. Accordingly, H2 S deficiency has been associated with several disorders, and many chemotypes of H2 S-releasing agents have been developed as potential therapeutic tools for diseases related with impaired H2 S production/activity. Some of these compounds are in advanced clinical trials. Presently, the pivotal role of H2 S in modulating the inflammatory response and proinflammatory cytokine cascade is well recognized, and the usefulness of some H2 S-donors for the treatment of different forms of acute lung inflammation (due to infectious and non-infectious etiologies) has been reported. More recent evidence is also unravelling several mechanisms of action which may account for antiviral effects of this gasotransmitter. Noteworthy, some preliminary clinical results suggest an inverse relationship between endogenous H2 S levels and severity of COVID-19 disease. Therefore, repurposing of H2 S-releasing drugs may be worthy of investigation as potential therapeutic opportunities for treatment of COVID-19 disease.

PMID: 32783196 [PubMed - as supplied by publisher]

Asoprisnil, a Selective Progesterone Receptor Modulator (SPRM), Inhibits Melanosome Export in B16F10 Cells and HEMn-DP Melanocytes.

Molecules. 2020 Aug 06;25(16):

Authors: Goenka S, R Simon S

Abstract
Previous studies have reported that estrogen hormone promotes melanogenesis while progesterone inhibits it. A selective estrogen receptor modulator (SERM), tamoxifen, has been shown to promote melanogenesis; however, to date, there have been no reports on the effects of a selective progesterone receptor modulator (SPRM) on melanogenesis. In the present study, we hypothesized that asoprisnil (AP), a SPRM, inhibits melanogenesis. AP was tested for cytotoxicity to B16F10 mouse melanoma cells for screening the nontoxic concentrations using MTS cytotoxicity assay. Extracellular and intracellular melanin levels were estimated at nontoxic concentrations of AP. To evaluate the direct effect of AP on tyrosinase enzyme, tyrosinase activity and copper chelating activities were measured. Next, the effects of AP on melanogenesis were tested in normal human melanocytes, neonatal, darkly pigmented (HEMn-DP). Our results demonstrate that AP was nontoxic at a concentration range of 10-50 μM in B16F10 cells; AP at 50 μM significantly suppressed extracellular melanin levels comparable to kojic acid at 500 μM, with no significant effect on intracellular melanin levels. The mechanism of melanogenesis inhibition was studied to assess if AP downregulated tyrosinase activity in cell lysates or in a cell-free system. However, AP was found to increase intracellular tyrosinase activity without any effect on tyrosinase enzyme activity or copper chelating activity in a cell-free system, indicating that AP inhibits melanogenesis by mechanisms other than direct effects on tyrosinase enzyme activity. The capacity of AP to inhibit melanosome export was further validated in HEMn-DP cells; AP significantly suppressed dendricity at concentrations of 20 and 30 μM in the absence of effects on melanin synthesis or intracellular tyrosinase activity. In addition, AP was nontoxic to human keratinocytes (HaCaT) at these concentrations, validating its safety for topical use. Taken together, our preliminary results demonstrate that AP might be repurposed as a candidate therapeutic for treatment of hyperpigmentation disorders via a unique mechanism, which encompasses a selective inhibition of melanosome export.

PMID: 32781695 [PubMed - in process]

In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication.

Sci Rep. 2020 08 04;10(1):13093

Authors: Touret F, Gilles M, Barral K, Nougairède A, van Helden J, Decroly E, de Lamballerie X, Coutard B

Abstract
A novel coronavirus, named SARS-CoV-2, emerged in 2019 in China and rapidly spread worldwide. As no approved therapeutics exists to treat COVID-19, the disease associated to SARS-Cov-2, there is an urgent need to propose molecules that could quickly enter into clinics. Repurposing of approved drugs is a strategy that can bypass the time-consuming stages of drug development. In this study, we screened the PRESTWICK CHEMICAL LIBRARY composed of 1,520 approved drugs in an infected cell-based assay. The robustness of the screen was assessed by the identification of drugs that already demonstrated in vitro antiviral effect against SARS-CoV-2. Thereby, 90 compounds were identified as positive hits from the screen and were grouped according to their chemical composition and their known therapeutic effect. Then EC50 and CC50 were determined for a subset of 15 compounds from a panel of 23 selected drugs covering the different groups. Eleven compounds such as macrolides antibiotics, proton pump inhibitors, antiarrhythmic agents or CNS drugs emerged showing antiviral potency with 2 < EC50 ≤ 20 µM. By providing new information on molecules inhibiting SARS-CoV-2 replication in vitro, this study provides information for the selection of drugs to be further validated in vivo. Disclaimer: This study corresponds to the early stages of antiviral development and the results do not support by themselves the use of the selected drugs to treat SARS-CoV-2 infection.

PMID: 32753646 [PubMed - indexed for MEDLINE]

The pandemic pipeline.

Nat Biotechnol. 2020 05;38(5):523-532

Authors: Hodgson J

PMID: 32203293 [PubMed - indexed for MEDLINE]

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 2020/08/12

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.

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 2020/08/11

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.

Taking the brake off the immune system: Hypotheses, trials, tribulations, and the evolving discipline of clinical immunopharmacology.

Br J Clin Pharmacol. 2020 Aug 07;:

Authors: Martin JH, Lewis LD

PMID: 32770557 [PubMed - as supplied by publisher]

Network-based modeling of drug effects on disease module in systemic sclerosis.

Sci Rep. 2020 Aug 07;10(1):13393

Authors: Kim KJ, Moon SJ, Park KS

Abstract
The network-based proximity between drug targets and disease genes can provide novel insights regarding the repercussions, interplay, and repositioning of drugs in the context of disease. Current understanding and treatment for reversing of the fibrotic process is limited in systemic sclerosis (SSc). We have developed a network-based analysis for drug effects that takes into account the human interactome network, proximity measures between drug targets and disease-associated genes, genome-wide gene expression and disease modules that emerge through pertinent analysis. Currently used and potential drugs showed a wide variation in proximity to SSc-associated genes and distinctive proximity to the SSc-relevant pathways, depending on their class and targets. Tyrosine kinase inhibitors (TyKIs) approach disease gene through multiple pathways, including both inflammatory and fibrosing processes. The SSc disease module includes the emerging molecular targets and is in better accord with the current knowledge of the pathophysiology of the disease. In the disease-module network, the greatest perturbing activity was shown by nintedanib, followed by imatinib, dasatinib, and acetylcysteine. Suppression of the SSc-relevant pathways and alleviation of the skin fibrosis was remarkable in the inflammatory subsets of the SSc patients receiving TyKI therapy. Our results show that network-based drug-disease proximity offers a novel perspective into a drug's therapeutic effect in the SSc disease module. This could be applied to drug combinations or drug repositioning, and be helpful guiding clinical trial design and subgroup analysis.

PMID: 32770109 [PubMed - as supplied by publisher]

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 2020/08/09

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 2020/08/09

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 2020/08/08

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.

Ion Channels as Therapeutic Targets for Viral Infections: Further Discoveries and Future Perspectives.

Viruses. 2020 Aug 03;12(8):

Authors: Charlton FW, Pearson HM, Hover S, Lippiat JD, Fontana J, Barr JN, Mankouri J

Abstract
Ion channels play key roles in almost all facets of cellular physiology and have emerged as key host cell factors for a multitude of viral infections. A catalogue of ion channel-blocking drugs have been shown to possess antiviral activity, some of which are in widespread human usage for ion channel-related diseases, highlighting new potential for drug repurposing. The emergence of ion channel-virus interactions has also revealed the intriguing possibility that channelopathies may explain some commonly observed virus induced pathologies. This field is rapidly evolving and an up-to-date summary of new discoveries can inform future perspectives. We herein discuss the role of ion channels during viral lifecycles, describe the recently identified ion channel drugs that can inhibit viral infections, and highlight the potential contribution of ion channels to virus-mediated disease.

PMID: 32756358 [PubMed - in process]

Endothelial activation and dysfunction in metabolic syndrome, type 2 diabetes and coronavirus disease 2019.

J Int Med Res. 2020 Jul;48(7):300060520939746

Authors: Hayden MR

Abstract
The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 infection is a serious global concern. Increased morbidity and mortality is associated with older age, male gender, cardiovascular disease, diabetes, and smoking. As COVID-19 spreads from coastal borders, both state to state and country to country, our understanding of its pathophysiology has evolved. Age and type 2 diabetes mellitus (T2DM) play especially important roles in COVID-19 progression. T2DM is an age-related disease associated with metabolic syndrome, obesity, insulin resistance (hyperinsulinemia), hyperlipidemia, hypertension, hyperglycemia, and endothelial activation and dysfunction. This review evaluates the relationships and intersection between endothelial cell activation and dysfunction in T2DM and COVID-19. COVID-19 induces multiple injuries of the terminal bronchioles and alveolar blood-gas barrier and associated ultrastructural tissue remodeling. COVID-19 may unmask multiple vulnerabilities associated with T2DM including damage to the endothelial glycocalyx and multiple end-organ macro and microvascular diseases. Unmasking existing vulnerabilities in diabetic patients with COVID-19 is important. Globally, we must come together to better understand why T2DM is associated with increased COVID-19 morbidity and mortality.

PMID: 32722979 [PubMed - indexed for MEDLINE]

In Silico Insights into the SARS CoV-2 Main Protease Suggest NADH Endogenous Defences in the Control of the Pandemic Coronavirus Infection.

Viruses. 2020 07 26;12(8):

Authors: Martorana A, Gentile C, Lauria A

Abstract
COVID-19 is a pandemic health emergency faced by the entire world. The clinical treatment of the severe acute respiratory syndrome (SARS) CoV-2 is currently based on the experimental administration of HIV antiviral drugs, such as lopinavir, ritonavir, and remdesivir (a nucleotide analogue used for Ebola infection). This work proposes a repurposing process using a database containing approximately 8000 known drugs in synergy structure- and ligand-based studies by means of the molecular docking and descriptor-based protocol. The proposed in silico findings identified new potential SARS CoV-2 main protease (MPRO) inhibitors that fit in the catalytic binding site of SARS CoV-2 MPRO. Several selected structures are NAD-like derivatives, suggesting a relevant role of these molecules in the modulation of SARS CoV-2 infection in conditions of cell chronic oxidative stress. Increased catabolism of NAD(H) during protein ribosylation in the DNA damage repair process may explain the greater susceptibility of the elderly population to the acute respiratory symptoms of COVID-19. The molecular modelling studies proposed herein agree with this hypothesis.

PMID: 32722574 [PubMed - indexed for MEDLINE]

8 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 2020/08/06

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.

Repurposing anticancer drugs for the treatment of idiopathic pulmonary fibrosis and antifibrotic drugs for the treatment of cancer: state of the art.

Curr Med Chem. 2020 Jul 30;:

Authors: Paliogiannis P, Fois SS, Fois AG, Cossu A, Palmieri G, Pintus G

Abstract
Idiopathic pulmonary fibrosis (IPF) is an aggressive pulmonary disease which shares several molecular, patho-physiological and clinical aspects with lung cancer, including high mortality rates. The antifibrotic drugs Nintedanib and Pirfenidone have been recently introduced in clinical practice for the treatment of IPF. Nintedanib is also used for the treatment of several malignancies, including non-small cell lung cancer (NSCLC) in combination with Docetaxel, while Pirfenidone showed some anti-neoplastic effects in preclinical studies. On the other hand, novel targeted agents and immunotherapies have been introduced in the last decade for the treatment of NSCLC, and some of them showed anti-fibrotic properties in recent studies. These evidences, based on the common pathophysiological backgrounds of IPF and lung cancer, make possible the mutual or combined use of anti-fibrotic and anti-neoplastic drugs to treat these highly lethal diseases. The aim of the present review is to depict the current scientific landscape regarding the repurposing of anti-neoplastic drugs in IPF and antifibrotic drugs in lung cancer, and to identify future research perspectives on the topic.

PMID: 32748739 [PubMed - as supplied by publisher]

In silico drug design and molecular docking studies targeting Akt1 (RAC-alpha serine/threonine-protein kinase) and Akt2 (RAC-beta serine/threonine-protein kinase) proteins and investigation of CYP (cytochrome P450) inhibitors against MAOB (monoamine oxidase B) for OSCC (oral squamous cell carcinoma) treatment.

J Biomol Struct Dyn. 2020 Aug 04;:1-13

Authors: Sharif Siam MK, Sarker A, Sayeem MMS

Abstract
The overexpression of Akt1 (RAC-alpha serine/threonine-protein Kinase) and Akt2 (RAC-beta serine/threonine-protein Kinase) is a hallmark of Oral Squamous Cell Carcinoma (OSCC). Because of the elevated frequency of OSCC occurrence in South Asian countries, novel therapeutic approaches are indispensable. Drugs that inhibit the overexpression of Akt1 and Akt2 proteins in Akt pathway and do not cause reduced expression of MAOB can be leads for OSCC treatment. In this study, Akt1, Akt2 and MAOB were targeted and 100 CYP inhibitors were screened through several in silico approaches and Galuteolin and Linarin were identified as potential leads for OSCC treatment as they inhibited Akt1 proteins with strong binding affinities of -12.3 and -11.5 kcal/mol respectively and also Akt2 proteins with strong binding affinities of -11.4 and -11.1 kcal/mol respectively, but they did not inhibit MAOB. Decreased expression of MAOB in tissues causes OSCC but overexpression is also responsible for other types of diseases and cancers. From the investigation of CYP inhibitors against MAOB, five CYP inhibitors- Diosmetin, Acacetin, Epicatechin, Eriodictyol and Capillin have expressed inhibitory action against MAOB without any interference with Akt1 and Akt2. This study mainly represents that Galuteolin and Linarin in the Akt pathway can be perceived for OSCC treatment and other five CYP inhibitors - Diosmetin, Acacetin, Epicatechin, Eriodictyol and Capillin for the treatment of other diseases and cancers caused by overexpression of MAOB. ADMET properties of CYP inhibitors obtained from admetSAR 2.0 and were compared with reference drugs for validation. Communicated by Ramaswamy H. Sarma.

PMID: 32746771 [PubMed - as supplied by publisher]

Newly Emergent 2019-nCoV and New Uses of an Old Medicine, Doxycycline; A Hypothesis.

Infect Disord Drug Targets. 2020;20(3):351

Authors: Tong TRS

PMID: 32696730 [PubMed - indexed for MEDLINE]

Novel Drugs Targeting the SARS-CoV-2/COVID-19 Machinery.

Curr Top Med Chem. 2020;20(16):1423-1433

Authors: Sternberg A, McKee DL, Naujokat C

Abstract
Like other human pathogenic viruses, coronavirus SARS-CoV-2 employs sophisticated macromolecular machines for viral host cell entry, genome replication and protein processing. Such machinery encompasses SARS-CoV-2 envelope spike (S) glycoprotein required for host cell entry by binding to the ACE2 receptor, viral RNA-dependent RNA polymerase (RdRp) and 3-chymotrypsin-like main protease (3Clpro/Mpro). Under the pressure of the accelerating COVID-19 pandemic caused by the outbreak of SARS-CoV-2 in Wuhan, China in December 2019, novel and repurposed drugs were recently designed and identified for targeting the SARS-CoV-2 reproduction machinery, with the aim to limit the spread of SARS-CoV-2 and morbidity and mortality due to the COVID-19 pandemic.

PMID: 32416679 [PubMed - indexed for MEDLINE]