scholarly journals Repurposable Drugs for SARS-CoV-2 and Influenza Sepsis with scRNA-Seq Data Targeting Post-Transcription Modifications

2021 ◽  
Author(s):  
Zhihan Wang ◽  
Kai Guo ◽  
Pan Gao ◽  
Qinqin Pu ◽  
Changlong Li ◽  
...  
Keyword(s):  
Influenza A ◽  
Viral Infections ◽  
Human Life ◽  
Drug Repurposing ◽  
Post Translational Modification ◽  
Integrated Network ◽  
Ssrna Virus ◽  
Public Data ◽  
Approved Drugs ◽  
Fda Approved Drugs

Abstract Coronavirus disease 2019 (COVID-19) has been impacting almost every part of human life worldwide, posing a massive threat to human health. Due to the lack of time for new drug discovery and the urgent need for rapid disease control, drug repurposing presents a quick and effective alternative to finding therapeutics to reduce mortality. To identify potentially repurposable drugs, we employed a systematic approach to mine candidates from U.S. FDA-approved drugs and preclinical small-molecule compounds by integrating the gene expression perturbation data for chemicals from the Library of Integrated Network-Based Cellular Signatures project with a publicly available single-cell RNA sequencing dataset from mild and severe COVID-19 patients (GEO: GSE145926, public data available and accessed on April 22, 2020). We identified 281 FDA-approved drugs that have the potential to be effective against SARS-CoV-2 infection, 16 of which are currently undergoing clinical trials to evaluate their efficacy against COVID-19. We experimentally tested and demonstrated the inhibitory effects of tyrphostin-AG-1478 and brefeldin-a, two chemical inhibitors of glycosylation (a post-translational modification) on the replication of the single-stranded ribonucleic acid (ssRNA) virus influenza A virus as well as on the transcription and translation of host cell cytokines and their regulators (IFNs and ISGs). In conclusion, we have identified and experimentally validated repurposable anti-SARS-CoV-2 and IAV drugs using a systems biology approach, which may have the potential for treating these viral infections and their complications (sepsis).

Structural Basis of Antisickling Effects of Selected FDA Approved Drugs: A Drug Repurposing Study

2018 ◽  
Vol 14 (2) ◽  
pp. 106-116 ◽  
Author(s):  
Olujide O. Olubiyi ◽  
Maryam O. Olagunju ◽  
James O. Oni ◽  
Abidemi O. Olubiyi
Keyword(s):  
Drug Repurposing ◽  
Structural Basis ◽  
Approved Drugs ◽  
Fda Approved Drugs

scholarly journals Screening of an FDA-Approved Library for Novel Drugs against Y. pestis

Antibiotics ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 40
Author(s):  
David Gur ◽  
Theodor Chitlaru ◽  
Emanuelle Mamroud ◽  
Ayelet Zauberman
Keyword(s):  
Drug Repurposing ◽  
Mortality Rates ◽  
Systematic Screening ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Therapy Initiation ◽  
Novel Drugs ◽  
Resistant Strains ◽  
Approved Drugs ◽  
Fda Approved Drugs

Yersinia pestis is a Gram-negative pathogen that causes plague, a devastating disease that kills millions worldwide. Although plague is efficiently treatable by recommended antibiotics, the time of antibiotic therapy initiation is critical, as high mortality rates have been observed if treatment is delayed for longer than 24 h after symptom onset. To overcome the emergence of antibiotic resistant strains, we attempted a systematic screening of Food and Drug Administration (FDA)-approved drugs to identify alternative compounds which may possess antibacterial activity against Y. pestis. Here, we describe a drug-repurposing approach, which led to the identification of two antibiotic-like activities of the anticancer drugs bleomycin sulfate and streptozocin that have the potential for designing novel antiplague therapy approaches. The inhibitory characteristics of these two drugs were further addressed as well as their efficiency in affecting the growth of Y. pestis strains resistant to doxycycline and ciprofloxacin, antibiotics recommended for plague treatment.

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

In Silico Modeling of FDA-Approved Drugs for Discovery of Anticandida Agents: A Drug-Repurposing Approach

2019 ◽  
pp. 463-526 ◽  
Author(s):  
Sohini Chakraborti ◽  
Gayatri Ramakrishnan ◽  
Narayanaswamy Srinivasan
Keyword(s):  
In Silico ◽  
Drug Repurposing ◽  
In Silico Modeling ◽  
Approved Drugs ◽  
Fda Approved Drugs

scholarly journals Target-Centered Drug Repurposing Predictions of Human Angiotensin-Converting Enzyme 2 (ACE2) and Transmembrane Protease Serine Subtype 2 (TMPRSS2) Interacting Approved Drugs for Coronavirus Disease 2019 (COVID-19) Treatment through a Drug-Target Interaction Deep Learning Model

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1325
Author(s):  
Yoonjung Choi ◽  
Bonggun Shin ◽  
Keunsoo Kang ◽  
Sungsoo Park ◽  
Bo Ram Beck
Keyword(s):  
Deep Learning ◽  
Angiotensin Converting Enzyme ◽  
Drug Target ◽  
Expression Profiles ◽  
Drug Repurposing ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Target Interaction ◽  
Approved Drugs ◽  
Fda Approved Drugs

Previously, our group predicted commercially available Food and Drug Administration (FDA) approved drugs that can inhibit each step of the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using a deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI). Unfortunately, additional clinically significant treatment options since the approval of remdesivir are scarce. To overcome the current coronavirus disease 2019 (COVID-19) more efficiently, a treatment strategy that controls not only SARS-CoV-2 replication but also the host entry step should be considered. In this study, we used MT-DTI to predict FDA approved drugs that may have strong affinities for the angiotensin-converting enzyme 2 (ACE2) receptor and the transmembrane protease serine 2 (TMPRSS2) which are essential for viral entry to the host cell. Of the 460 drugs with Kd of less than 100 nM for the ACE2 receptor, 17 drugs overlapped with drugs that inhibit the interaction of ACE2 and SARS-CoV-2 spike reported in the NCATS OpenData portal. Among them, enalaprilat, an ACE inhibitor, showed a Kd value of 1.5 nM against the ACE2. Furthermore, three of the top 30 drugs with strong affinity prediction for the TMPRSS2 are anti-hepatitis C virus (HCV) drugs, including ombitasvir, daclatasvir, and paritaprevir. Notably, of the top 30 drugs, AT1R blocker eprosartan and neuropsychiatric drug lisuride showed similar gene expression profiles to potential TMPRSS2 inhibitors. Collectively, we suggest that drugs predicted to have strong inhibitory potencies to ACE2 and TMPRSS2 through the DTI model should be considered as potential drug repurposing candidates for COVID-19.

Recent Drug-Repurposing-Driven Advances in the Discovery of Novel Antibiotics

2019 ◽  
Vol 26 (28) ◽  
pp. 5363-5388 ◽  
Author(s):  
Ananda Kumar Konreddy ◽  
Grandhe Usha Rani ◽  
Kyeong Lee ◽  
Yongseok Choi
Keyword(s):  
Drug Discovery ◽  
Bacterial Infections ◽  
De Novo ◽  
Genetic Disorder ◽  
Antibacterial Properties ◽  
Drug Repurposing ◽  
Global Public Health ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Novel Antibiotics

: Drug repurposing is a safe and successful pathway to speed up the novel drug discovery and development processes compared with de novo drug discovery approaches. Drug repurposing uses FDA-approved drugs and drugs that failed in clinical trials, which have detailed information on potential toxicity, formulation, and pharmacology. Technical advancements in the informatics, genomics, and biological sciences account for the major success of drug repurposing in identifying secondary indications of existing drugs. Drug repurposing is playing a vital role in filling the gap in the discovery of potential antibiotics. Bacterial infections emerged as an ever-increasing global public health threat by dint of multidrug resistance to existing drugs. This raises the urgent need of development of new antibiotics that can effectively fight multidrug-resistant bacterial infections (MDRBIs). The present review describes the key role of drug repurposing in the development of antibiotics during 2016–2017 and of the details of recently FDA-approved antibiotics, pipeline antibiotics, and antibacterial properties of various FDA-approved drugs of anti-cancer, anti-fungal, anti-hyperlipidemia, antiinflammatory, anti-malarial, anti-parasitic, anti-viral, genetic disorder, immune modulator, etc. Further, in view of combination therapies with the existing antibiotics, their potential for new implications for MDRBIs is discussed. The current review may provide essential data for the development of quick, safe, effective, and novel antibiotics for current needs and suggest acuity in its effective implications for inhibiting MDRBIs by repurposing existing drugs.

scholarly journals Repurposing of Linagliptin Similar FDA Approved Drugs as Antidiabetic Agents

2021 ◽  
Vol 10 (4) ◽  
pp. 2766-2776
Keyword(s):  
Metabolic Diseases ◽  
Drug Repurposing ◽  
Binding Energies ◽  
New Drugs ◽  
Epidemic Disease ◽  
Global Epidemic ◽  
Dpp Iv ◽  
Epidemiology Data ◽  
Approved Drugs ◽  
Fda Approved Drugs

Diabetes mellitus is considered a global epidemic disease and is one of the metabolic diseases affecting individuals irrespective of age, sex, and race. According to WHO epidemiology data, the DM prevalence globally has risen from 4.7% to 8.5 % from 1980 to 2014. The discovery of new drugs has become more challenging for the pharmaceutical companies even though major investment has made in the conventional drug discovery approach. To overcome this obstacle, drug repurposing is an emerging field of development where an existing drug is tested for treatment. Successful repurposing of zidovudine, minoxidil, sildenafil, celecoxib, aspirin, and topiramate are reported for respective diseases. The present study focused on the computational approach to fetch the favorable drugs from the pool of FDA approved drugs against diabetes. Initially, structure similarity studies were carried out by using the template structure of standard DPP-IV inhibitor, Linagliptin. About 26 drugs have shown similarity, and the other 14 drugs filtered by Pass Online binding energies are determined by molecular docking at the binding site of DPP-IV (PDB ID 2i78). Among these, pranlukast and mirabegron have shown good binding interactions with dock scores of -13.81 and -13.06.

scholarly journals Sulfisoxazole does not inhibit the secretion of small extracellular vesicles

2020 ◽  
Author(s):  
Pamali Fonseka ◽  
Sai V Chitti ◽  
Rahul Sanwlani ◽  
Suresh Mathivanan
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Breast Cancer Cells ◽  
Drug Repurposing ◽  
Tumor Burden ◽  
Immunocompetent Mouse ◽  
Approved Drugs ◽  
Fda Approved Drugs

AbstractRecently, the study by Im et al. focused on blocking the release of extracellular vesicles (EVs) by cancer cells, as a strategy to block metastasis, by deploying a drug repurposing screen. Upon screening the library of FDA approved drugs in breast cancer cells in vitro, the authors reported the ability of the antibiotic Sulfisoxazole (SFX) in inhibiting EV biogenesis and secretion. SFX was also effective in reducing breast primary tumor burden and blocking metastasis in immunocompromised and immunocompetent mouse models. As we seek a compound to block EV biogenesis and secretion in our current in vivo studies, we intended to use SFX and hence performed in vitro characterization as the first step. However, treatment of two cancer cells with SFX did not reduce the amount of EVs as reported by the authors.

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