scholarly journals COVID-19 Knowledge Extractor (COKE): A Tool and a Web Portal to Extract Drug - Target Protein Associations from the CORD-19 Corpus of Scientific Publications on COVID-19

2020 ◽  
Author(s):  
Daniel Korn ◽  
Vera Pervitsky ◽  
Tesia Bobrowski ◽  
Vinicius Alves ◽  
Charles Schmitt ◽  
...  
Keyword(s):  
Web Application ◽  
Drug Target ◽  
Drug Repurposing ◽  
Research Literature ◽  
Target Protein ◽  
Scientific Publications ◽  
Biological Targets ◽  
Drug Candidates ◽  
Short Period ◽  
Approved Drugs

<p><b>Objective:</b> The COVID-19 pandemic has catalyzed a widespread effort to identify drug candidates and biological targets of relevance to SARS-COV-2 infection, which resulted in large numbers of publications on this subject. We have built the <b><u>CO</u></b>VID-19 <b><u>K</u></b>nowledge <b><u>E</u></b>xtractor (COKE), a web application to extract, curate, and annotate essential drug-target relationships from the research literature on COVID-19 to assist drug repurposing efforts.</p> <p><b>Materials and Methods:</b> SciBiteAI ontological tagging of the COVID Open Research Dataset (CORD-19), a repository of COVID-19 scientific publications, was employed to identify drug-target relationships. Entity identifiers were resolved through lookup routines using UniProt and DrugBank. A custom algorithm was used to identify co-occurrences of protein and drug terms, and confidence scores were calculated for each entity pair.</p> <p><b>Results:</b> COKE processing of the current CORD-19 database identified about 3,000 drug-protein pairs, including 29 unique proteins and 500 investigational, experimental, and approved drugs. Some of these drugs are presently undergoing clinical trials for COVID-19.</p> <p><b>Discussion:</b> The rapidly evolving situation concerning the COVID-19 pandemic has resulted in a dramatic growth of publications on this subject in a short period. These circumstances call for methods that can condense the literature into the key concepts and relationships necessary for insights into SARS-CoV-2 drug repurposing. </p> <p><b>Conclusion:</b> The COKE repository and web application deliver key drug - target protein relationships to researchers studying SARS-CoV-2. COKE portal may provide comprehensive and critical information on studies concerning drug repurposing against COVID-19. COKE is freely available at <a href="https://coke.mml.unc.edu/">https://coke.mml.unc.edu/</a> and the code is available at <a href="https://github.com/DnlRKorn/CoKE">https://github.com/DnlRKorn/CoKE</a>. </p>

scholarly journals COVID-19 Knowledge Extractor (COKE): A Tool and a Web Portal to Extract Drug - Target Protein Associations from the CORD-19 Corpus of Scientific Publications on COVID-19

2020 ◽  
Author(s):  
Daniel Korn ◽  
Vera Pervitsky ◽  
Tesia Bobrowski ◽  
Vinicius Alves ◽  
Charles Schmitt ◽  
...  
Keyword(s):  
Web Application ◽  
Drug Target ◽  
Drug Repurposing ◽  
Research Literature ◽  
Target Protein ◽  
Scientific Publications ◽  
Biological Targets ◽  
Drug Candidates ◽  
Short Period ◽  
Approved Drugs

<p><b>Objective:</b> The COVID-19 pandemic has catalyzed a widespread effort to identify drug candidates and biological targets of relevance to SARS-COV-2 infection, which resulted in large numbers of publications on this subject. We have built the <b><u>CO</u></b>VID-19 <b><u>K</u></b>nowledge <b><u>E</u></b>xtractor (COKE), a web application to extract, curate, and annotate essential drug-target relationships from the research literature on COVID-19 to assist drug repurposing efforts.</p> <p><b>Materials and Methods:</b> SciBiteAI ontological tagging of the COVID Open Research Dataset (CORD-19), a repository of COVID-19 scientific publications, was employed to identify drug-target relationships. Entity identifiers were resolved through lookup routines using UniProt and DrugBank. A custom algorithm was used to identify co-occurrences of protein and drug terms, and confidence scores were calculated for each entity pair.</p> <p><b>Results:</b> COKE processing of the current CORD-19 database identified about 3,000 drug-protein pairs, including 29 unique proteins and 500 investigational, experimental, and approved drugs. Some of these drugs are presently undergoing clinical trials for COVID-19.</p> <p><b>Discussion:</b> The rapidly evolving situation concerning the COVID-19 pandemic has resulted in a dramatic growth of publications on this subject in a short period. These circumstances call for methods that can condense the literature into the key concepts and relationships necessary for insights into SARS-CoV-2 drug repurposing. </p> <p><b>Conclusion:</b> The COKE repository and web application deliver key drug - target protein relationships to researchers studying SARS-CoV-2. COKE portal may provide comprehensive and critical information on studies concerning drug repurposing against COVID-19. COKE is freely available at <a href="https://coke.mml.unc.edu/">https://coke.mml.unc.edu/</a> and the code is available at <a href="https://github.com/DnlRKorn/CoKE">https://github.com/DnlRKorn/CoKE</a>. </p>

scholarly journals Drug Repurposing Techniques in Viral Diseases

2021 ◽  
Author(s):  
Ran Zhang ◽  
Rick Oerlemans ◽  
Chao Wang ◽  
Lili Zhang ◽  
Matthew R. Groves
Keyword(s):  
Drug Development ◽  
Economic Activity ◽  
Molecular Mechanisms ◽  
Drug Repurposing ◽  
Rapid Identification ◽  
Drug Candidates ◽  
Short Period ◽  
Approved Drugs ◽  
Antiviral Medications ◽  
High Degree

Since the advent of the twentieth century, several severe virus outbreaks have occurred—H1N1 (1918), H2N2 (1957), H3N2 (1968), H1N1 (2009) and recently COVID-19 (2019)—all of which have posed serious challenges to public health. Therefore, rapid identification of efficacious antiviral medications is of ongoing paramount importance in combating such outbreaks. Due to the long cycle of drug development, not only in the development of a “safe” medication but also in mandated and extensive (pre)clinical trials before a drug can be safely licensed for use, it is difficult to access effective and safe novel antivirals. This is of particular importance in addressing infectious disease in appropriately short period of time to limit stress to ever more interlinked societal infrastructures; including interruptions to economic activity, supply routes as well as the immediate impact on health care. Screening approved drugs or drug candidates for antiviral activity to address emergent diseases (i.e. repurposing) provides an elegant and effective strategy to circumvent this problem. As such treatments (in the main) have already received approval for their use in humans, many of their limitations and contraindications are well known, although efficacy against new diseases must be shown in appropriate laboratory trials and clinical studies. A clear in this approach in the case of antivirals is the “relative” simplicity and a high degree of conservation of the molecular mechanisms that support viral replication—which improves the chances for a functional antiviral to inhibit replication in a related viral species. However, recent experiences have shown that while repurposing has the potential to identify such cases, great care must be taken to ensure a rigourous scientific underpinning for repurposing proposals. Here, we present a brief explanation of drug repurposing and its approaches, followed by an overview of recent viral outbreaks and associated drug development. We show how drug repurposing and combination approaches have been used in viral infectious diseases, highlighting successful cases. Special emphasis has been placed on the recent COVID-19 outbreak, and its molecular mechanisms and the role repurposing can/has play(ed) in the discovery of a treatment.

scholarly journals Translational and Clinical Pharmacology Considerations in Drug Repurposing for X-linked Adrenoleukodystrophy-A Rare Peroxisomal Disorder

2021 ◽  
Author(s):  
Julianne Tieu ◽  
Siddhee Sahasrabudhe ◽  
Paul Orchard ◽  
James Cloyd ◽  
Reena Kartha
Keyword(s):  
Drug Target ◽  
Drug Targets ◽  
Drug Repurposing ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Drug Candidates ◽  
Target Patient Population ◽  
Site Of Action ◽  
Repurposed Drugs ◽  
Gait Disturbances ◽  
Spastic Quadriparesis

X-linked adrenoleukodystrophy (X-ALD) is an inherited, neurodegenerative rare disease that can result in devastating symptoms of blindness, gait disturbances, and spastic quadriparesis due to progressive demyelination. Typically, the disease progresses rapidly, causing death within the first decade of life. With limited treatments available, efforts to determine an effective therapy that can alter disease progression or mitigate symptoms have been undertaken for many years, particularly through drug repurposing. Repurposing has generally been guided through clinical experience and small trials. At this time, none of the drug candidates have been approved for use, which may be due, in part, to the lack of pharmacokinetic/pharmacodynamic (PK/PD) information on the repurposed medications in the target patient population. Greater consideration for the disease pathophysiology, drug pharmacology, and potential drug-target interactions, specifically at the site of action, would improve drug repurposing and facilitate development. Although there is a good understanding of X-ALD pathophysiology, the absence of information on drug targets, pharmacokinetics, and pharmacodynamics hinders the repurposing of drugs for this condition. Incorporating advanced translational and clinical pharmacological approaches in preclinical studies and early stages clinical trials will improve the success of repurposed drugs for X-ALD as well as other rare diseases.

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.

scholarly journals Drug repurposing using transcriptome sequencing and virtual drug screening in a patient with glioblastoma

2020 ◽  
Author(s):  
Mohamed E. M. Saeed ◽  
Onat Kadioglu ◽  
Henry Johannes Greten ◽  
Adem Yildirim ◽  
Katharina Mayr ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Treatment Options ◽  
Drug Repurposing ◽  
Sequencing Data ◽  
Survival Times ◽  
Chemical Library ◽  
Ki 67 ◽  
Drug Candidates ◽  
Egfr Expression ◽  
Approved Drugs

SummaryBackground Precision medicine and drug repurposing are attractive strategies, especially for tumors with worse prognosis. Glioblastoma is a highly malignant brain tumor with limited treatment options and short survival times. We identified novel BRAF (47-438del) and PIK3R1 (G376R) mutations in a glioblastoma patient by RNA-sequencing. Methods The protein expression of BRAF and PIK3R1 as well as the lack of EGFR expression as analyzed by immunohistochemistry corroborated RNA-sequencing data. The expression of additional markers (AKT, SRC, mTOR, NF-κB, Ki-67) emphasized the aggressiveness of the tumor. Then, we screened a chemical library of > 1500 FDA-approved drugs and > 25,000 novel compounds in the ZINC database to find established drugs targeting BRAF47-438del and PIK3R1-G376R mutated proteins. Results Several compounds (including anthracyclines) bound with higher affinities than the control drugs (sorafenib and vemurafenib for BRAF and PI-103 and LY-294,002 for PIK3R1). Subsequent cytotoxicity analyses showed that anthracyclines might be suitable drug candidates. Aclarubicin revealed higher cytotoxicity than both sorafenib and vemurafenib, whereas idarubicin and daunorubicin revealed higher cytotoxicity than LY-294,002. Liposomal formulations of anthracyclines may be suitable to cross the blood brain barrier. Conclusions In conclusion, we identified novel small molecules via a drug repurposing approach that could be effectively used for personalized glioblastoma therapy especially for patients carrying BRAF47-438del and PIK3R1-G376R mutations.

scholarly journals Computational guided approach for drug repurposing against SARS-CoV-2

2021 ◽  
Author(s):  
Jigisha Anand ◽  
Tanmay Ghildiyal ◽  
Aakanksha Madhwal ◽  
Rishabh Bhatt ◽  
Devvret Verma ◽  
...  
Keyword(s):  
Drug Targets ◽  
De Novo ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Computational Docking ◽  
Drug Candidates ◽  
Docking Tool ◽  
Inhibitory Potential ◽  
Approved Drugs ◽  
Tract Infections

Background: In the current SARS-CoV-2 outbreak, drug repositioning emerges as a promising approach to develop efficient therapeutics in comparison to de novo drug development. The present investigation screened 130 US FDA-approved drugs including hypertension, cardiovascular diseases, respiratory tract infections (RTI), antibiotics and antiviral drugs for their inhibitory potential against SARS-CoV-2. Materials & methods: The molecular drug targets against SARS-CoV-2 proteins were determined by the iGEMDOCK computational docking tool. The protein homology models were generated through SWISS Model workspace. The pharmacokinetics of all the ligands was determined by ADMET analysis. Results: The study identified 15 potent drugs exhibiting significant inhibitory potential against SARS-CoV-2. Conclusion: Our investigation has identified possible repurposed drug candidates to improve the current modus operandi of the treatment given to COVID-19 patients.

scholarly journals Integrated Docking and Enhanced Sampling Based Selection of Repurposing Drugs for SARS-CoV-2 by Targeting Host Dependent Factors

2020 ◽  
Author(s):  
Amit Kumawat ◽  
Sadanandam Namsani ◽  
Debabrata Pramanik ◽  
Sudip Roy ◽  
Jayant K. Singh
Keyword(s):  
Regulatory Protein ◽  
Drug Repurposing ◽  
Md Simulations ◽  
Free Energy Calculations ◽  
High Throughput Analysis ◽  
Drug Candidates ◽  
Global Pandemic ◽  
Therapeutic Uses ◽  
Approved Drugs ◽  
Fda Approved Drugs

Since the onset of global pandemic, the most focused research currently in progress is the development of vaccine candidates and clinical trials of existing FDA approved drugs for other relevant diseases, in order to repurpose them for the COVID-19. Here, we investigate the drug repurposing strategies to counteract the coronavirus infection which involves several potential targetable host proteins involved in viral replication and disease progression. We report the high throughput analysis of literature-derived repurposing drug candidates that can be used to target the genetic regulators known to interact with viral proteins based on experimental and interactome studies. In this work we have performed integrated molecular docking followed by molecular dynamics (MD) simulations and free energy calculations through an expedite insilico process where the number of screened candidates reduces sequentially at every step based on physicochemical information. We elucidate that in addition to the pre-clinical and FDA approved drugs that targets specific regulatory proteins, a range of chemical compounds (Nafamostat, Chloramphenicol, Ponatinib) binds to the other gene transcription and translation regulatory protein with higher affinity and may harbour potential for therapeutic uses.<br>

Drug Discovery by Drug Repurposing: Combating COVID-19 in the 21st Century

2020 ◽  
Vol 20 ◽  
Author(s):  
Nitesh Sanghai ◽  
Kashfia Shafiq ◽  
Geoffrey K. Tranmer
Keyword(s):  
Drug Discovery ◽  
Drug Repurposing ◽  
Compassionate Use ◽  
Drug Candidates ◽  
Working Day ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Day By Day ◽  
Potential Use

: Due to the rapidly developing nature of the current COVID-19 outbreak and its almost immediate humanitarian and economic toll, coronavirus drug discovery efforts have largely focused on generating potential COVID-19 drug candidates as quickly as possible. Globally, scientists are working day and night to find the best possible solution to treat the deadly virus. During the first few months of 2020, the SARS-CoV-2 outbreak quickly developed into a pandemic, with a mortality rate that was increasing at an exponential rate day by day. As a result, scientists have turned to a drug repurposing approach, to rediscover the potential use and benefits of existing approved drugs. Currently, there is no single drug approved by the U.S. Food and Drug Administration (FDA), for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously known as 2019-nCoV) that causes COVID-19. Based on only in-vitro studies, several active drugs are already in the clinical pipeline, made possible by following the compassionate use of medicine protocols. This method of repurposing and the use of existing molecules like Remdesivir (GS-5734), Chloroquine, Hydroxychloroquine, etc. has proven to be a landmark in the field of drug rediscovery. In this review article we will discuss the repurposing of medicines for treating the deadly novel coronavirus (SARS-CoV-2).

scholarly journals Drug Repurposing of Approved Drugs Elbasvir, Ledipasvir, Paritaprevir, Velpatasvir, Antrafenine and Ergotamine for Combating COVID19

2020 ◽  
Author(s):  
Vishal Mevada ◽  
Pravin Dudhagara ◽  
Himani Gandhi ◽  
Nilam Vaghamshi ◽  
Urvisha Beladiya ◽  
...  
Keyword(s):  
Protein Structures ◽  
Drug Repurposing ◽  
Drug Candidates ◽  
Sequential Screening ◽  
Drug Molecules ◽  
Single Target ◽  
Approved Drugs ◽  
Hiv Drugs ◽  
Anti Hiv ◽  
Country Office

<p>Pneumonia of unknown cause detected in Wuhan, China was first reported to the WHO Country Office in China on 31 December 2019. The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020. Currently, there is no Vaccine against COVID-19 pandemic and infection is spreading worldwide vary rapidly there is an exigent requirement of practicable drug treatment. Drug repurposing is one of the most promising approaches for that. Many reports are available with <i>in silico</i> drug repurposing but the majority of them engrossed on a single target. The present study aimed at screening the approved against Covid19 protein and extract the combination of operational comprehensively. A total of 1735 drug molecules against all COVID19 protein structures and sequential screening recognize the better potential of anti-HCV drugs over anti-HIV drugs. The study designated Elbasvir, Ledipasvir, Paritaprevir, Velpatasvir, Antrafenine Ergotamin as promising drug candidates for covid19 treatment. The computational analysis also reveled the better potential of proposed drugs over the currently used drug combination for COVID19 drugs. </p>

scholarly journals In-Silico FDA-Approved Drug Repurposing to Find the Possible Treatment of Coronavirus Disease-19 (COVID-19)

2020 ◽  
Author(s):  
Kumar Sharp ◽  
Dr. Shubhangi Dange
Keyword(s):  
In Silico ◽  
Drug Target ◽  
Drug Repurposing ◽  
Target Interaction ◽  
Compound Libraries ◽  
Anti Cancer ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Large Compound ◽  
Better Than

Identification of potential drug-target interaction for approved drugs serves as the basis of repurposing drugs. Studies have shown polypharmacology as common phenomenon. In-silico approaches help in screening large compound libraries at once which could take years in a laboratory. We screened a library of 1050 FDA-approved drugs against spike glycoprotein of SARS-CoV2 in-silico. Anti-cancer drugs have shown good binding affinity which is much better than hydroxychloroquine and arbidol. We have also introduced a hypothesis named “Bump” hypothesis which and be developed further in field of computational biology.

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