Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Drug Repurposing Approach, Potential Drugs, and Novel Drug Targets for COVID-19 Treatment.

ABSTRACT: Novel coronavirus first appeared in Wuhan, China, in December 2019, and it speedily expanded globally. Some medications which are used to treat other diseases seem to be effective in treating COVID-19 even without explicit support. The existing drugs that are summarized in this review primarily focused on therapeutic agents that possessed activity against other RNA viruses such as MERS-CoV and SARS-CoV. Drug repurposing or repositioning is a promising field in drug discovery that identifies new therapeutic opportunities for existing drugs such as corticosteroids, RNA-dependent RNA polymerase inhibitors, interferons, protease inhibitors, ivermectin, melatonin, teicoplanin, and some others. A search for new drug/drug targets is underway. Thus, blocking coronavirus structural protein, targeting viral enzyme, dipeptidyl peptidase 4, and membrane fusion blocker (angiotensin-converting enzyme 2 and CD147 inhibitor) are major sites based on molecular targets for the management of COVID-19 infection. The possible impact of biologics for the management of COVID19 is promising and includes a wide variety of options such as cytokines, nucleic acid-based therapies targeting virus gene expression, bioengineered and vectored antibodies, and various types of vaccines. This review demonstrates that the available data are not sufficient to suggest any treatment for the eradication of COVID-19 to be used at the clinical level. This article aims to review the roles of existing drugs and drug targets for COVID-19 treatment.

SUBMITTER: Kifle ZD

PROVIDER: S-EPMC8063850 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Drug repurposing approach to combating coronavirus: Potential drugs and drug targets.

Project description:In the past two decades, three highly pathogenic human coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus, and, recently, SARS-CoV-2, have caused pandemics of severe acute respiratory diseases with alarming morbidity and mortality. Due to the lack of specific anti-CoV therapies, the ongoing pandemic of coronavirus disease 2019 (COVID-19) poses a great challenge to clinical management and highlights an urgent need for effective interventions. Drug repurposing is a rapid and feasible strategy to identify effective drugs for combating this deadly infection. In this review, we summarize the therapeutic CoV targets, focus on the existing small molecule drugs that have the potential to be repurposed for existing and emerging CoV infections of the future, and discuss the clinical progress of developing small molecule drugs for COVID-19.

| S-EPMC8044022 | biostudies-literature

Drug repurposing approach to fight COVID-19.

Project description:Currently, there are no treatment options available for the deadly contagious disease, coronavirus disease 2019 (COVID-19). Drug repurposing is a process of identifying new uses for approved or investigational drugs and it is considered as a very effective strategy for drug discovery as it involves less time and cost to find a therapeutic agent in comparison to the de novo drug discovery process. The present review will focus on the repurposing efficacy of the currently used drugs against COVID-19 and their mechanisms of action, pharmacokinetics, dosing, safety, and their future perspective. Relevant articles with experimental studies conducted in-silico, in-vitro, in-vivo, clinical trials in humans, case reports, and news archives were selected for the review. Number of drugs such as remdesivir, favipiravir, ribavirin, lopinavir, ritonavir, darunavir, arbidol, chloroquine, hydroxychloroquine, tocilizumab and interferons have shown inhibitory effects against the SARS-CoV2 in-vitro as well as in clinical conditions. These drugs either act through virus-related targets such as RNA genome, polypeptide packing and uptake pathways or target host-related pathways involving angiotensin-converting enzyme-2 (ACE2) receptors and inflammatory pathways. Using the basic knowledge of viral pathogenesis and pharmacodynamics of drugs as well as using computational tools, many drugs are currently in pipeline to be repurposed. In the current scenario, repositioning of the drugs could be considered the new avenue for the treatment of COVID-19.

| S-EPMC7474498 | biostudies-literature

Repurposing Anti-Cancer Drugs for COVID-19 Treatment.

Project description:The novel coronavirus disease 2019 (COVID-19) pandemic has caused catastrophic damage to human life across the globe along with social and financial hardships. According to the Johns Hopkins University Coronavirus Resource Center, more than 41.3 million people worldwide have been infected, and more than 1,133,000 people have died as of October 22, 2020. At present, there is no available vaccine and a scarcity of efficacious therapies. However, there is tremendous ongoing effort towards identifying effective drugs and developing novel vaccines. Early data from Adaptive COVID-19 Treatment Trials (ACTT) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) and compassionate use study have shown promise for remdesivir, leading to emergency authorization by the Food and Drug Administration (FDA) for treatment of hospitalized COVID-19 patients. However, several randomized studies have now shown no benefit or increased adverse events associated with remdesivir treatment. Drug development is a time-intensive process and requires extensive safety and efficacy evaluations. In contrast, drug repurposing is a time-saving and cost-effective drug discovery strategy geared towards using existing drugs instead of de novo drug discovery. Treatments for cancer and COVID-19 often have similar goals of controlling inflammation, inhibiting cell division, and modulating the host microenvironment to control the disease. In this review, we focus on anti-cancer drugs that can potentially be repurposed for COVID-19 and are currently being tested in clinical trials.

| S-EPMC7680713 | biostudies-literature

Artificial intelligence approach fighting COVID-19 with repurposing drugs.

Project description:BackgroundThe ongoing COVID-19 pandemic has caused more than 193,825 deaths during the past few months. A quick-to-be-identified cure for the disease will be a therapeutic medicine that has prior use experiences in patients in order to resolve the current pandemic situation before it could become worsening. Artificial intelligence (AI) technology is hereby applied to identify the marketed drugs with potential for treating COVID-19.MethodsAn AI platform was established to identify potential old drugs with anti-coronavirus activities by using two different learning databases; one consisted of the compounds reported or proven active against SARS-CoV, SARS-CoV-2, human immunodeficiency virus, influenza virus, and the other one containing the known 3C-like protease inhibitors. All AI predicted drugs were then tested for activities against a feline coronavirus in in vitro cell-based assay. These assay results were feedbacks to the AI system for relearning and thus to generate a modified AI model to search for old drugs again.ResultsAfter a few runs of AI learning and prediction processes, the AI system identified 80 marketed drugs with potential. Among them, 8 drugs (bedaquiline, brequinar, celecoxib, clofazimine, conivaptan, gemcitabine, tolcapone, and vismodegib) showed in vitro activities against the proliferation of a feline infectious peritonitis (FIP) virus in Fcwf-4 cells. In addition, 5 other drugs (boceprevir, chloroquine, homoharringtonine, tilorone, and salinomycin) were also found active during the exercises of AI approaches.ConclusionHaving taken advantages of AI, we identified old drugs with activities against FIP coronavirus. Further studies are underway to demonstrate their activities against SARS-CoV-2 in vitro and in vivo at clinically achievable concentrations and doses. With prior use experiences in patients, these old drugs if proven active against SARS-CoV-2 can readily be applied for fighting COVID-19 pandemic.

| S-EPMC7227517 | biostudies-literature

Drug Repurposing for the Treatment of COVID-19: A Knowledge Graph Approach.

Project description:Identifying effective drug treatments for COVID-19 is essential to reduce morbidity and mortality. Although a number of existing drugs have been proposed as potential COVID-19 treatments, effective data platforms and algorithms to prioritize drug candidates for evaluation and application of knowledge graph for drug repurposing have not been adequately explored. A COVID-19 knowledge graph by integrating 14 public bioinformatic databases containing information on drugs, genes, proteins, viruses, diseases, symptoms and their linkages is developed. An algorithm is developed to extract hidden linkages connecting drugs and COVID-19 from the knowledge graph, to generate and rank proposed drug candidates for repurposing as treatments for COVID-19 by integrating three scores for each drug: motif scores, knowledge graph PageRank scores, and knowledge graph embedding scores. The knowledge graph contains over 48 000 nodes and 13 37 000 edges, including 13 563 molecules in the DrugBank database. From the 5624 molecules identified by the motif-discovery algorithms, ranking results show that 112 drug molecules had the top 2% scores, of which 50 existing drugs with other indications approved by health administrations reported. The proposed drug candidates serve to generate hypotheses for future evaluation in clinical trials and observational studies.

| S-EPMC8212091 | biostudies-literature

Transcriptomics-based drug repurposing approach identifies novel drugs against sorafenib-resistant hepatocellular carcinoma

Project description:Hepatocellular carcinoma (HCC) is frequently diagnosed in patients with late-stage disease who are ineligible for curative surgical therapies. Furthermore, the majority of patients become resistant to sorafenib. Recently, computational methods for drug repurposing have shown great promise to accelerate the discovery of new uses for existing drugs. In order to identify novel drugs for use against sorafenib resistant (SR)-HCC, we employed a transcriptomics-based drug repurposing method termed connectivity mapping. We conducted a comprehensive analysis of available in vitro and in vivo gene signatures of (SR)-HCC, and generated our own in vitro model using the Huh7 HCC cell line. We compared coverage of SR-HCC gene signatures across seven patient-derived HCC gene expression datasets, and observed that patients harboring the Huh7 SR-HCC gene signature had significantly reduced survival. Utilizing the Huh7 SR-HCC gene signature, we applied connectivity mapping to drug-induced gene expression profiles (n= 3,740 drugs) in the HepG2 HCC cell line from the LINCS database in order to find drugs that could oppose sorafenib resistance. We validated the use of two non-receptor tyrosine kinase inhibitors, dasatinib and fostamatinib, to reduce viability of sorafenib-resistant HCC cells and confirmed up-regulated activity of Src family kinases, the targets of dasatinib, in our SR-HCC models. We prospectively validated predicted gene expression changes in fostamatinib treated Huh7-SR via RNA-seq analysis.

2019-09-01 | GSE113005 | GEO

A multimodal deep learning-based drug repurposing approach for treatment of COVID-19.

Project description:Recently, various computational methods have been proposed to find new therapeutic applications of the existing drugs. The Multimodal Restricted Boltzmann Machine approach (MM-RBM), which has the capability to connect the information about the multiple modalities, can be applied to the problem of drug repurposing. The present study utilized MM-RBM to combine two types of data, including the chemical structures data of small molecules and differentially expressed genes as well as small molecules perturbations. In the proposed method, two separate RBMs were applied to find out the features and the specific probability distribution of each datum (modality). Besides, RBM was used to integrate the discovered features, resulting in the identification of the probability distribution of the combined data. The results demonstrated the significance of the clusters acquired by our model. These clusters were used to discover the medicines which were remarkably similar to the proposed medications to treat COVID-19. Moreover, the chemical structures of some small molecules as well as dysregulated genes' effect led us to suggest using these molecules to treat COVID-19. The results also showed that the proposed method might prove useful in detecting the highly promising remedies for COVID-19 with minimum side effects. All the source codes are accessible using https://github.com/LBBSoft/Multimodal-Drug-Repurposing.git.

| S-EPMC7525234 | biostudies-literature

COVID-19: molecular targets, drug repurposing and new avenues for drug discovery.

Project description:Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious infection that may break the healthcare system of several countries. Here, we aimed at presenting a critical view of ongoing drug repurposing efforts for COVID-19 as well as discussing opportunities for development of new treatments based on current knowledge of the mechanism of infection and potential targets within. Finally, we also discuss patent protection issues, cost effectiveness and scalability of synthetic routes for some of the most studied repurposing candidates since these are key aspects to meet global demand for COVID-19 treatment.

| S-EPMC7534958 | biostudies-literature

Host transcriptome-guided drug repurposing for COVID-19 treatment: a meta-analysis based approach.

Project description:BackgroundCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a pandemic by the World Health Organization, and the identification of effective therapeutic strategy is a need of the hour to combat SARS-CoV-2 infection. In this scenario, the drug repurposing approach is widely used for the rapid identification of potential drugs against SARS-CoV-2, considering viral and host factors.MethodsWe adopted a host transcriptome-based drug repurposing strategy utilizing the publicly available high throughput gene expression data on SARS-CoV-2 and other respiratory infection viruses. Based on the consistency in expression status of host factors in different cell types and previous evidence reported in the literature, pro-viral factors of SARS-CoV-2 identified and subject to drug repurposing analysis based on DrugBank and Connectivity Map (CMap) using the web tool, CLUE.ResultsThe upregulated pro-viral factors such as TYMP, PTGS2, C1S, CFB, IFI44, XAF1, CXCL2, and CXCL3 were identified in early infection models of SARS-CoV-2. By further analysis of the drug-perturbed expression profiles in the connectivity map, 27 drugs that can reverse the expression of pro-viral factors were identified, and importantly, twelve of them reported to have anti-viral activity. The direct inhibition of the PTGS2 gene product can be considered as another therapeutic strategy for SARS-CoV-2 infection and could suggest six approved PTGS2 inhibitor drugs for the treatment of COVID-19. The computational study could propose candidate repurposable drugs against COVID-19, and further experimental studies are required for validation.

| S-EPMC7293190 | biostudies-literature

COVID-19: Drug Targets and Potential Treatments.

Project description:Currently, humans are immersed in a pandemic caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which threatens public health worldwide. To date, no drug or vaccine has been approved to treat the severe disease caused by this coronavirus, COVID-19. In this paper, we will focus on the main virus-based and host-based targets that can guide efforts in medicinal chemistry to discover new drugs for this devastating disease. In principle, all CoV enzymes and proteins involved in viral replication and the control of host cellular machineries are potentially druggable targets in the search for therapeutic options for SARS-CoV-2. This Perspective provides an overview of the main targets from a structural point of view, together with reported therapeutic compounds with activity against SARS-CoV-2 and/or other CoVs. Also, the role of innate immune response to coronavirus infection and the related therapeutic options will be presented.

| S-EPMC7323060 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data