scholarly journals Network-based Drug Repurposing for Human Coronavirus

2020 ◽  
Author(s):  
Yadi Zhou ◽  
Yuan Hou ◽  
Jiayu Shen ◽  
Yin Huang ◽  
William Martin ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Drug Targets ◽  
De Novo ◽  
Antiviral Drug ◽  
Drug Repurposing ◽  
Drug Combinations ◽  
Human Protein ◽  
High Morbidity ◽  
Potential Drug ◽  
Protein Interactome

AbstractHuman Coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle east respiratory syndrome coronavirus (MERS-CoV), and 2019 novel coronavirus (2019-nCoV), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV. Drug repurposing, represented as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV-host interactome and drug targets in the human protein-protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV has the highest nucleotide sequence identity with SARS-CoV (79.7%) among the six other known pathogenic HCoVs. Specifically, the envelope and nucleocapsid proteins of 2019-nCoV are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV. Using network proximity analyses of drug targets and known HCoV-host interactions in the human protein-protein interactome, we computationally identified 135 putative repurposable drugs for the potential prevention and treatment of HCoVs. In addition, we prioritized 16 potential anti-HCoV repurposable drugs (including melatonin, mercaptopurine, and sirolimus) that were further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. Finally, we showcased three potential drug combinations (including sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the ‘Complementary Exposure’ pattern: the targets of the drugs both hit the HCoV-host subnetwork, but target separate neighborhoods in the human protein-protein interactome network. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations toward future clinical trials for HCoVs.

scholarly journals Evaluation of Drug Repositioning by Molecular Docking of Pharmaceutical Resources to Identification of Potential SARS-CoV-2 Viral Inhibitors

2022 ◽  
Author(s):  
Fatemeh Hosseini ◽  
Mehrdad Azin ◽  
Hamideh Ofoghi ◽  
Tahereh Alinejad
Keyword(s):  
Molecular Docking ◽  
Drug Discovery ◽  
In Silico ◽  
De Novo ◽  
Drug Repositioning ◽  
Antiviral Drug ◽  
Drug Repurposing ◽  
Future Perspective

Unfortunately, to date, there is no approved specific antiviral drug treatment against COVID-19. Due to the costly and time-consuming nature of the de novo drug discovery and development process, in recent days, the computational drug repositioning method has been highly regarded for accelerating the drug-discovery process. The selection of drug target molecule(s), preparation of an approved therapeutics agent library, and in silico evaluation of their affinity to the subjected target(s) are the main steps of a molecular docking-based drug repositioning process, which is the most common computational drug re-tasking process. In this chapter, after a review on origin, pathophysiology, molecular biology, and drug development strategies against COVID-19, recent advances, challenges as well as the future perspective of molecular docking-based drug repositioning for COVID-19 are discussed. Furthermore, as a case study, the molecular docking-based drug repurposing process was planned to screen the 3CLpro inhibitor(s) among the nine Food and Drug Administration (FDA)-approved antiviral protease inhibitors. The results demonstrated that Fosamprenavir had the highest binding affinity to 3CLpro and can be considered for more in silico, in vitro, and in vivo evaluations as an effective repurposed anti-COVID-19 drug.

scholarly journals SAveRUNNER: an R-based tool for drug repurposing

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Giulia Fiscon ◽  
Paola Paci
Keyword(s):  
Drug Discovery ◽  
Drug Targets ◽  
De Novo ◽  
Herd Immunity ◽  
Drug Repurposing ◽  
Human Interactome ◽  
Off Label ◽  
Disease Associations ◽  
Associated Proteins ◽  
Novel Coronavirus

Abstract Background Currently, no proven effective drugs for the novel coronavirus disease COVID-19 exist and despite widespread vaccination campaigns, we are far short from herd immunity. The number of people who are still vulnerable to the virus is too high to hamper new outbreaks, leading a compelling need to find new therapeutic options devoted to combat SARS-CoV-2 infection. Drug repurposing represents an effective drug discovery strategy from existing drugs that could shorten the time and reduce the cost compared to de novo drug discovery. Results We developed a network-based tool for drug repurposing provided as a freely available R-code, called SAveRUNNER (Searching off-lAbel dRUg aNd NEtwoRk), with the aim to offer a promising framework to efficiently detect putative novel indications for currently marketed drugs against diseases of interest. SAveRUNNER predicts drug–disease associations by quantifying the interplay between the drug targets and the disease-associated proteins in the human interactome through the computation of a novel network-based similarity measure, which prioritizes associations between drugs and diseases located in the same network neighborhoods. Conclusions The algorithm was successfully applied to predict off-label drugs to be repositioned against the new human coronavirus (2019-nCoV/SARS-CoV-2), and it achieved a high accuracy in the identification of well-known drug indications, thus revealing itself as a powerful tool to rapidly detect potential novel medical indications for various drugs that are worth of further investigation. SAveRUNNER source code is freely available at https://github.com/giuliafiscon/SAveRUNNER.git, along with a comprehensive user guide.

Sitagliptin: a potential drug for the treatment of SARS-CoV-2?

2020 ◽  
Author(s):  
Sanaa Bardaweel
Keyword(s):  
Clinical Trials ◽  
Drug Discovery ◽  
Antimalarial Drug ◽  
Drug Repurposing ◽  
Spike Protein ◽  
Diabetic Patients ◽  
Potential Drug ◽  
Chemokine Production ◽  
Drug Discovery And Development ◽  
Sequence Identity

Recently, an outbreak of fatal coronavirus, SARS-CoV-2, has emerged from China and is rapidly spreading worldwide. As the coronavirus pandemic rages, drug discovery and development become even more challenging. Drug repurposing of the antimalarial drug chloroquine and its hydroxylated form had demonstrated apparent effectiveness in the treatment of COVID-19 associated pneumonia in clinical trials. SARS-CoV-2 spike protein shares 31.9% sequence identity with the spike protein presents in the Middle East Respiratory Syndrome Corona Virus (MERS-CoV), which infects cells through the interaction of its spike protein with the DPP4 receptor found on macrophages. Sitagliptin, a DPP4 inhibitor, that is known for its antidiabetic, immunoregulatory, anti-inflammatory, and beneficial cardiometabolic effects has been shown to reverse macrophage responses in MERS-CoV infection and reduce CXCL10 chemokine production in AIDS patients. We suggest that Sitagliptin may be beneficial alternative for the treatment of COVID-19 disease especially in diabetic patients and patients with preexisting cardiovascular conditions who are already at higher risk of COVID-19 infection.

Recent Advances in Drug Repurposing for Parkinson’s Disease

2019 ◽  
Vol 26 (28) ◽  
pp. 5340-5362 ◽  
Author(s):  
Xin Chen ◽  
Giuseppe Gumina ◽  
Kristopher G. Virga
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Discovery ◽  
De Novo ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Cost Effective ◽  
New Drugs ◽  
Recent Advances ◽  
Clinical Drugs

:As a long-term degenerative disorder of the central nervous system that mostly affects older people, Parkinson’s disease is a growing health threat to our ever-aging population. Despite remarkable advances in our understanding of this disease, all therapeutics currently available only act to improve symptoms but cannot stop the disease progression. Therefore, it is essential that more effective drug discovery methods and approaches are developed, validated, and used for the discovery of disease-modifying treatments for Parkinson’s disease. Drug repurposing, also known as drug repositioning, or the process of finding new uses for existing or abandoned pharmaceuticals, has been recognized as a cost-effective and timeefficient way to develop new drugs, being equally promising as de novo drug discovery in the field of neurodegeneration and, more specifically for Parkinson’s disease. The availability of several established libraries of clinical drugs and fast evolvement in disease biology, genomics and bioinformatics has stimulated the momentums of both in silico and activity-based drug repurposing. With the successful clinical introduction of several repurposed drugs for Parkinson’s disease, drug repurposing has now become a robust alternative approach to the discovery and development of novel drugs for this disease. In this review, recent advances in drug repurposing for Parkinson’s disease will be discussed.

scholarly journals Genomics-driven drug discovery based on disease-susceptibility genes

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Kyuto Sonehara ◽  
Yukinori Okada
Keyword(s):  
Drug Discovery ◽  
Drug Targets ◽  
Disease Susceptibility ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Drug Repurposing ◽  
Susceptibility Genes ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Disease Associations

AbstractGenome-wide association studies have identified numerous disease-susceptibility genes. As knowledge of gene–disease associations accumulates, it is becoming increasingly important to translate this knowledge into clinical practice. This challenge involves finding effective drug targets and estimating their potential side effects, which often results in failure of promising clinical trials. Here, we review recent advances and future perspectives in genetics-led drug discovery, with a focus on drug repurposing, Mendelian randomization, and the use of multifaceted omics data.

Dengue Structural Proteins as Antiviral Drug Targets: Current Status in the Drug Discovery & Development

2021 ◽  
pp. 113527
Author(s):  
Akshatha H. S ◽  
Gurubasavaraj V. Pujar ◽  
Arun Kumar Sethu ◽  
Meduri Bhagyalalitha ◽  
Manisha Singh
Keyword(s):  
Drug Discovery ◽  
Drug Targets ◽  
Antiviral Drug ◽  
Structural Proteins ◽  
Current Status

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 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.

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