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 2020/10/27

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.

Understanding Severe Acute Respiratory Syndrome Coronavirus 2 Replication to Design Efficient Drug Combination Therapies.

Intervirology. 2020 Oct 23;:1-8

Authors: Ortega JT, Zambrano JL, Jastrzebska B, Liprandi F, Rangel HR, Pujol FH

Abstract
BACKGROUND: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its disease CO-VID-19 has strongly encouraged the search for antiviral compounds. Most of the evaluated drugs against SARS-CoV-2 derive from drug repurposing of Food and Drug Administration-approved molecules. These drugs have as target three major processes: (1) early stages of virus-cell interaction, (2) viral proteases, and (3) the viral RNA-dependent RNA polymerase.
SUMMARY: This review focused on the basic principles of virology and pharmacology to understand the importance of early stages of virus-cell interaction as therapeutic targets and other main processes vital for SARS-CoV-2 replication. Furthermore, we focused on describing the main targets associated with SARS-CoV-2 antiviral therapy and the rationale of drug combinations for efficiently suppressing viral replication. Key Messages: We hypothesized that blocking of both entry mechanisms could allow a more effective antiviral effect compared to the partial results obtained with chloroquine or its derivatives alone. This approach, already used to achieve an antiviral effect higher than that offered by every single drug administered separately, has been successfully applied in several viral infections such as HIV and HCV. This review will contribute to expanding the perception of the possible therapeutic targets in SARS-CoV-2 infection and highlight the benefits of using combination therapies.

PMID: 33099545 [PubMed - as supplied by publisher]

Artificial intelligence in drug discovery and development.

Drug Discov Today. 2020 Oct 21;:

Authors: Paul D, Sanap G, Shenoy S, Kalyane D, Kalia K, Tekade RK

Abstract
Artificial Intelligence (AI) has recently started to gear-up its application in various sectors of the society with the pharmaceutical industry as a front-runner beneficiary. This review highlights the impactful use of AI in diverse areas of the pharmaceutical sectors viz., drug discovery and development, drug repurposing, improving pharmaceutical productivity, clinical trials, etc. to name a few, thus reducing the human workload as well as achieving targets in a short period. Crosstalk on the tools and techniques utilized in enforcing AI, ongoing challenges, and ways to overcome them, along with the future of AI in the pharmaceutical industry, is also discussed.

PMID: 33099022 [PubMed - as supplied by publisher]

System biological investigations of hydroxychloroquine and azithromycin targets and their implications in QT interval prolongation.

Chem Biol Interact. 2020 Oct 21;:109299

Authors: Khan AA, Khan Z

Abstract
COVID-2019 pandemic is affecting people worldwide in the absence of an effective treatment strategy. Several suggestive therapeutic options through drug repurposing are recommended, but a complete consensus is not reached. A combination of Hydroxychloroquine (HCQ) and Azithromycin (AZM) has been widely tried and discussed but its administration has also led to potential adversities in patients. Studies are suggesting that most prominent adverse event with HCQ and AZM combination is QT interval prolongation. We studied interaction of HCQ with AZM and subsequent effect of this drug combination on QT interval prolongation. We performed system biological investigation of HCQ and AZM targets and screened important targets and pathways possibly involved in QT interval prolongation. The best core hub protein drug targets involved in QT interval prolongation were identified as HSP90AA1 exclusively associated with HCQ, while AKT1 exclusively associated with AZM. It was found that PI3K/Akt, VEGF, ERBB2 pathways must be given consideration for understanding the role of HCQ and AZM in QT interval prolongation. Conclusion: Computational methods have certain limitations based on source database coverage and prediction algorithms and therefore this data needs experimental correlation to draw final conclusion, but current findings screen targets for QT interval prolongation associated with HCQ and AZM. These proteins and pathways may provide ways to reduce this major risk associated with this combination.

PMID: 33098839 [PubMed - as supplied by publisher]

Alternative treatment of fungal infections: synergy with non-antifungal agents.

Mycoses. 2020 Oct 23;:

Authors: Rossato L, Dos Santos MC, Vitale RG, de Hoog S, Ishida K

Abstract
Fungal infections are responsible for high mortality rates in immunocompromised and high-risk surgical patients. Therapy failures during the last decades due to increasing multidrug resistance demand innovative strategies for novel and effective antifungal drugs. Synergistic combinations of antifungals with non-antifungal agents highlight a pragmatic strategy to reduce the development of drug resistance and potentially repurpose known compounds with other functions to bypass costly and time-consuming novel drug development.

PMID: 33098146 [PubMed - as supplied by publisher]

Functional network analysis reveals potential repurposing of β-blocker atenolol for pancreatic cancer therapy.

Daru. 2020 Oct 23;:

Authors: Hermawan A, Putri H, Utomo RY

Abstract
BACKGROUND: The survival rate of patients with pancreatic cancer is low; therefore, continuous discovery and development of novel pancreatic cancer drugs are required. Functional network analysis is an integrated bioinformatics approach based on gene, target, and disease networks interaction, and it is extensively used in drug discovery and development.
OBJECTIVE: This study aimed to identify if atenolol, a selective adrenergic inhibitor, can be repurposed for the treatment of pancreatic cancer using functional network analysis.
METHODS: Direct target proteins (DTPs) and indirect target proteins (ITPs) were obtained from STITCH and STRING databases, respectively. Atenolol-mediated proteins (AMPs) were collected from DTPs and ITPs and further analyzed for gene ontology, KEGG pathway enrichment, genetic alterations, overall survival, and molecular docking.
RESULTS: We obtained 176 AMPs that consisted of 10 DTPs and 166 ITPs. Among the AMPs involved in the pancreatic cancer pathways, several AMPs such as MAPK1, RELA, MAPK8, STAT1, and STAT3 were identified. Genetic alterations in seven AMPs were identified in 0.9%-16% of patients. Patients with high mRNA levels of MAPK1, RELA, STAT3, GNB1, and MMP9 had significantly worse overall survival rates compared with patients with low expression. Molecular docking studies showed that RELA and MMP9 are potential target candidates of atenolol in the treatment of patients with pancreatic cancer.
CONCLUSION: In conclusion, atenolol can potentially be repurposed to target pancreatic cancer cells by modulating MMP9 and NF-κB signaling. The results of this study need to be further validated in vitro and in vivo.

PMID: 33098056 [PubMed - as supplied by publisher]

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 2020/10/24

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.

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 2020/10/23

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.

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 2020/10/22

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.

FPSC-DTI: drug-target interaction prediction based on feature projection fuzzy classification and super cluster fusion.

Mol Omics. 2020 Oct 21;:

Authors: Yu D, Liu G, Zhao N, Liu X, Guo M

Abstract
Identifying drug-target interactions (DTIs) is an important part of drug discovery and development. However, identifying DTIs is a complex process that is time consuming, costly, long, and often inefficient, with a low success rate, especially with wet-experimental methods. Computational methods based on drug repositioning and network pharmacology can effectively overcome these defects. In this paper, we develop a new fusion method, called FPSC-DTI, that fuses feature projection fuzzy classification (FP) and super cluster classification (SC) to predict DTI. As the experimental result, the mean percentile ranking (MPR) that was yielded by FPSC-DTI achieved 0.043, 0.084, 0.072, and 0.146 on enzyme, ion channel (IC), G-protein-coupled receptor (GPCR), and nuclear receptor (NR) datasets, respectively. And the AUC values exceeded 0.969 over all four datasets. Compared with other methods, FPSC-DTI obtained better predictive performance and became more robust.

PMID: 33084702 [PubMed - as supplied by publisher]

Associations between genetically predicted protein levels and COVID-19 severity.

J Infect Dis. 2020 Oct 21;:

Authors: Zhu J, Wu C, Wu L

Abstract
It is critical to identify potential causal targets for SARS-coronavirus 2, which may guide drug repurposing options. We assessed the associations between genetically predicted protein levels and COVID-19 severity. Leveraging data from The COVID-19 host genetics initiative comparing 6,492 hospitalized COVID-19 patients and 1,012,809 controls, we identified 18 proteins with genetically predicted levels to be associated with COVID-19 severity at a false discovery rate of <0.05, including 12 that showed an association even after Bonferroni correction. Of the 18 proteins, six showed positive associations and 12 showed inverse associations. In conclusion, we identified 18 candidate proteins for COVID-19 severity.

PMID: 33083826 [PubMed - as supplied by publisher]

A Systems Biology Workflow for Drug and Vaccine Repurposing: Identifying Small-Molecule BCG Mimics to Reduce or Prevent COVID-19 Mortality.

Pharm Res. 2020 Oct 06;37(11):212

Authors: Hajjo R, Tropsha A

Abstract
PURPOSE: Coronavirus disease 2019 (COVID-19) is expected to continue to cause worldwide fatalities until the World population develops 'herd immunity', or until a vaccine is developed and used as a prevention. Meanwhile, there is an urgent need to identify alternative means of antiviral defense. Bacillus Calmette-Guérin (BCG) vaccine that has been recognized for its off-target beneficial effects on the immune system can be exploited to boast immunity and protect from emerging novel viruses.
METHODS: We developed and employed a systems biology workflow capable of identifying small-molecule antiviral drugs and vaccines that can boast immunity and affect a wide variety of viral disease pathways to protect from the fatal consequences of emerging viruses.
RESULTS: Our analysis demonstrates that BCG vaccine affects the production and maturation of naïve T cells resulting in enhanced, long-lasting trained innate immune responses that can provide protection against novel viruses. We have identified small-molecule BCG mimics, including antiviral drugs such as raltegravir and lopinavir as high confidence hits. Strikingly, our top hits emetine and lopinavir were independently validated by recent experimental findings that these compounds inhibit the growth of SARS-CoV-2 in vitro.
CONCLUSIONS: Our results provide systems biology support for using BCG and small-molecule BCG mimics as putative vaccine and drug candidates against emergent viruses including SARS-CoV-2.

PMID: 33025261 [PubMed - indexed for MEDLINE]

COVID-19: Underpinning Research for Detection, Therapeutics, and Vaccines Development.

Pharm Nanotechnol. 2020;8(4):323-353

Authors: Aljabali AAA, Bakshi HA, Satija S, Metha M, Prasher P, Ennab RM, Chellappan DK, Gupta G, Negi P, Goyal R, Sharma A, Mishra V, Dureja H, Dua K, Tambuwala MM

Abstract
BACKGROUND: The newly emerged coronavirus SARS-CoV-2, first reported in December 2019, has infected about five and a half million people globally and resulted in nearly 9063264 deaths until the 24th of June 2020. Nevertheless, the highly contagious virus has instigated an unimaginably rapid response from scientific and medical communities.
OBJECTIVES: Pioneering research on molecular mechanisms underlying the viral transmission, molecular pathogenicity, and potential treatments will be highlighted in this review. The development of antiviral drugs specific to SARS-CoV-2 is a complicated and tedious process. To accelerate scientific discoveries and advancement, researchers are consolidating available data from associated coronaviruses into a single pipeline, which can be readily made available to vaccine developers.
METHODS: In order to find studies evaluating the COVID-19 virus epidemiology, repurposed drugs and potential vaccines, web searches and bibliographical bases have been used with keywords that matches the content of this review.
RESULTS: The published results of SARS-CoV-2 structures and interactomics have been used to identify potential therapeutic candidates. We illustrate recent publications on SARS-CoV-2, concerning its molecular, epidemiological, and clinical characteristics, and focus on innovative diagnostics technologies in the production pipeline. This objective of this review is to enhance the comprehension of the unique characteristics of SARS-CoV-2 and strengthen future control measures.
Lay Summary: An innovative analysis is evaluating the nature of the COVID-19 pandemic. The aim is to increase knowledge of possible viral detection methods, which highlights several new technology limitations and advantages. We have assessed some drugs currently for patients (Lopinavir, Ritonavir, Anakinra and Interferon beta 1a), as the feasibility of COVID-19 specific antivirals is not presently known. The study explores the race toward vaccine development and highlights some significant trials and candidates in various clinical phases. This research addresses critical knowledge gaps by identifying repurposed drugs currently under clinical trials. Findings will be fed back rapidly to the researchers interested in COVID 19 and support the evidence and potential of possible therapeutics and small molecules with their mode of action.

PMID: 32811406 [PubMed - indexed for MEDLINE]

SARS-CoV-2 in patients on antiviral HBV and HCV therapy in Spain.

J Hepatol. 2020 11;73(5):1262-1263

Authors: Lens S, Miquel M, Mateos-Muñoz B, García-Samaniego J, Forns X

PMID: 32673740 [PubMed - indexed for MEDLINE]

26 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 2020/10/21

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.

31 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 2020/10/21

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.

37 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 2020/10/19

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 2020/10/14

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.

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 2020/10/13

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.

COVID-19: discovery, diagnostics and drug development.

J Hepatol. 2020 Oct 07;:

Authors: Asselah T, Durantel D, Pasmant E, Lau G, Schinazi RF

Abstract
An epidemic of acute respiratory syndrome (Covid-19) started in humans in Wuhan in 2019, and became a pandemic. Groups from China Identified and sequenced the virus responsible for COVID-19, named SARS-CoV-2, and determined that it was a novel coronavirus (CoV) that shared high sequence identity with bat- and pangolin-derived SARS-like CoVs, suggesting a zoonotic origin. SARS-CoV-2 is a member of Coronaviridae, a family of enveloped, positive-sense, single-stranded RNA viruses that infect a broad range of vertebrates. The rapid release of the sequence of the virus has allowed the development of diagnostic tools (e.g., RT-PCR). Additionally, serological tests can allow identification of persons who have been infected. In humans, CoVs tend to cause mild to moderate upper respiratory tract infections. The fatality rate is around 1-3% for infected persons. An acute respiratory distress syndrome (ARDS) likely due to an uncontrolled immune activation ("cytokine storm") occurs in patients with severe disease and poor prognosis. Risk factors for mortality include: advanced age, obesity, diabetes, hypertension and other comorbidities. Drug repurposing has been used to rapidly identify potential treatment for COVID-19, which could move quickly to phase-3. Better knowledge of the virus, its enzymes, will be mandatory to develop more potent and specific direct-acting antiviral agents (DAA). In the long term, a vaccine to prevent infection would be crucial; however even if successful it might not be available before 2021-22. To date, with the exception of intravenous Remdesivir and dexamethasone, which have modest effects in moderate to severe COVID-19, no strong clinical evidence supports the efficacy and safety of any other drugs against SARS-CoV-2. The aim of this review is to provide insights on the discovery of SARS-CoV-2, its virology, the diagnostic tools, and the ongoing drug discovery effort.

PMID: 33038433 [PubMed - as supplied by publisher]