Drug repositioning: A Unique Approach to Refurbish Drug Discovery

2021 ◽  
Vol 18 ◽  
Author(s):  
Mayura A Kale ◽  
Prashant B Shamkuwar ◽  
Vishnukant K Mourya ◽  
Aishwarya B Deshpande ◽  
Priyanka A Shelke
Keyword(s):  
Drug Discovery ◽  
Drug Repositioning ◽  
Cost Effective ◽  
Positive Outcomes ◽  
Computational Tools ◽  
Therapeutic Implications ◽  
Novel Drugs ◽  
Unique Approach ◽  
Approved Drugs

: Since a decade, it has been observed that there is remarkable decrease in the quantum of novel clinically approved drugsin spite of modernization in research and development process. We have highlighted repositioning of drugs as a methodology that has found new therapeutic implications for clinically approved drugs but with different indications. This can be considered as an upbringing strategy to deliver timely and cost-effective solutions which still needexplorationtoget over the shortage of number of novel drugs reaching market. This review focuses on activity-based drug repositioning approach, which is used to explore new uses of known drugs that are already approved for specific indications and are now being used for other indications on the basis ofthe fact that single drug interacts with multiple targets. It also includes current research trends related to drug repositioning which depends on strong knowledge of medicinal chemistry and involves elucidation of mechanisms of action and validation of novel targets. The review highlights theimportance totheusage of computational tools and databases of various forms for drug repositioning purposes which have enhanced the ability to pose reasonable and testable hypotheses. The critical nature of this aspect is obvious in cases where data gathered from in vitro or animal models do not confirm in subsequent clinical trials. Hence, considering positive outcomes of drug repositioning, it can be surmised that this approach can serve as promising one that can develop into a robust drug discovery strategy.

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 Targeting SARS-CoV-2 Polymerase with New Nucleoside Analogues

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3461
Author(s):  
Vasiliki Daikopoulou ◽  
Panagiotis Apostolou ◽  
Sofia Mourati ◽  
Ioanna Vlachou ◽  
Maria Gougousi ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Drug Repositioning ◽  
Nucleoside Analogues ◽  
In Vitro Assays ◽  
Rna Dependent Rna Polymerase ◽  
Sugar Moiety ◽  
The Family ◽  
Approved Drugs ◽  
Fda Approved Drugs

Despite the fact that COVID-19 vaccines are already available on the market, there have not been any effective FDA-approved drugs to treat this disease. There are several already known drugs that through drug repositioning have shown an inhibitory activity against SARS-CoV-2 RNA-dependent RNA polymerase. These drugs are included in the family of nucleoside analogues. In our efforts, we synthesized a group of new nucleoside analogues, which are modified at the sugar moiety that is replaced by a quinazoline entity. Different nucleobase derivatives are used in order to increase the inhibition. Five new nucleoside analogues were evaluated with in vitro assays for targeting polymerase of SARS-CoV-2.

scholarly journals Drug repositioning as a route to anti-malarial drug discovery: preliminary investigation of the in vitro anti-malarial efficacy of emetine dihydrochloride hydrate

2013 ◽  
Vol 12 (1) ◽  
pp. 359 ◽  
Author(s):  
Holly Matthews ◽  
Maryam Usman-Idris ◽  
Farid Khan ◽  
Martin Read ◽  
Niroshini Nirmalan
Keyword(s):  
Drug Discovery ◽  
Drug Repositioning ◽  
Preliminary Investigation

scholarly journals Fabrication of Planar Microelectrode Array Using Laser-Patterned ITO and SU-8

Micromachines ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1347
Author(s):  
Hee Soo Jeong ◽  
Seoyoung Hwang ◽  
Kyou Sik Min ◽  
Sang Beom Jun
Keyword(s):  
Indium Tin Oxide ◽  
Microelectrode Array ◽  
Cost Effective ◽  
Neural Recording ◽  
Different Types ◽  
Unique Approach ◽  
Impedance Monitoring ◽  
The Stability ◽  
Microfabrication Techniques

For several decades, microelectrode array (MEA) has been a powerful tool for in vitro neural electrophysiology because it provides a unique approach for monitoring the activity of a number of neurons over time. Due to the various applications of MEAs with different types of cells and tissues, there is an increasing need to customize the electrode designs. However, the fabrication of conventional MEAs requires several microfabrication procedures of deposition, etching, and photolithography. In this study, we proposed a simple fabrication method with a laser-patterned indium tin oxide (ITO) conductor and SU-8 photoresist insulation. Unlike in a conventional metal patterning process, only the outlines of ITO conductors are ablated by laser without removing background ITO. Insulation is achieved simply via SU-8 photolithography. The electrode sites are electroplated with iridium oxide (IrOX) to improve the electrochemical properties. The fabricated MEAs are electrochemically characterized and the stability of insulation is also confirmed by impedance monitoring for three weeks. Dissociated neurons of rat hippocampi are cultured on MEAs to verify the biocompatibility and the capacity for extracellular neural recording. The electrochemical and electrophysiological results with the fabricated MEAs are similar to those from conventional SiNX-insulated MEAs. Therefore, the proposed MEA with laser-patterned ITO and SU-8 is cost-effective and equivalently feasible compared with the conventional MEAs fabricated using thin-film microfabrication techniques.

scholarly journals Déjà vu: Stimulating Open Drug Discovery for SARS-CoV-2

2020 ◽  
Author(s):  
Sean Ekins ◽  
Melina Mottin ◽  
Paulo R. P. S. Ramos ◽  
Bruna K. P. Sousa ◽  
Bruno Junior Neves ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Ebola Virus ◽  
Antiviral Drug ◽  
Open Science ◽  
Virus Rna ◽  
Deja Vu ◽  
Déjà Vu ◽  
Approved Drugs

In the past decade we have seen two major Ebola virus outbreaks in Africa, the Zika virus in Brazil and the current outbreak of coronavirus disease which has been named "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). There is a strong sense of Déjà vu as the world is caught flat footed without effective treatments to administer to patients. Our team has been actively involved in several small molecule drug discovery efforts for the preceding virus outbreaks. In 2014 we used machine learning to identify 3 new molecules to test for the Ebola virus and these were subsequently shown to be active in vitro and in vivo. We have also been involved in open science approaches that leverage the community to help. In 2016 we launched the OpenZika project as an IBM World Community Grid Project that used distributed computing power of volunteers to dock large numbers of compounds into Zika and related flavivirus targets. This led us into several collaborations in which we validated computational predictions in vitro. With both of these initiatives there was some knowledge of the virus, many compounds had already been tested in the case of Ebola, whereas for Zika initially all we had was the virus RNA sequence. In the current SARS-CoV-2 outbreak, this was a completely new virus and the scientists in China and elsewhere have started from scratch. In the space of a few weeks since the outbreak is acknowledged to have started, there are now compounds suggested as active in vitro and molecules repurposed in clinical trials. While this has been impressive, we propose there may still be gaps in our approach to drug discovery for such outbreaks. There is an opportunity to repurpose additional approved drugs for this virus and we now suggest how these might be identified leveraging prior work on MERS-CoV, SARS-CoV and other viruses. We also describe some of the immense challenges and limitations of the open antiviral drug discovery approaches we have been involved in.

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 Lapatinib, Nilotinib and Lomitapide Inhibit Haemozoin Formation in Malaria Parasites

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1571 ◽  
Author(s):  
Ana Carolina C. de Sousa ◽  
Keletso Maepa ◽  
Jill M. Combrinck ◽  
Timothy J. Egan
Keyword(s):  
Experimental Evaluation ◽  
Antimalarial Activity ◽  
Drug Repositioning ◽  
Hit Rate ◽  
Docking Method ◽  
Electrostatic Similarity ◽  
Approved Drugs ◽  
Novel Structures ◽  
Antimalarial Action

With the continued loss of antimalarials to resistance, drug repositioning may have a role in maximising efficiency and accelerating the discovery of new antimalarial drugs. Bayesian statistics was previously used as a tool to virtually screen USFDA approved drugs for predicted β-haematin (synthetic haemozoin) inhibition and in vitro antimalarial activity. Here, we report the experimental evaluation of nine of the highest ranked drugs, confirming the accuracy of the model by showing an overall 93% hit rate. Lapatinib, nilotinib, and lomitapide showed the best activity for inhibition of β-haematin formation and parasite growth and were found to inhibit haemozoin formation in the parasite, providing mechanistic insights into their mode of antimalarial action. We then screened the USFDA approved drugs for binding to the β-haematin crystal, applying a docking method in order to evaluate its performance. The docking method correctly identified imatinib, lapatinib, nilotinib, and lomitapide. Experimental evaluation of 22 of the highest ranked purchasable drugs showed a 24% hit rate. Lapatinib and nilotinib were chosen as templates for shape and electrostatic similarity screening for lead hopping using the in-stock ChemDiv compound catalogue. The actives were novel structures worthy of future investigation. This study presents a comparison of different in silico methods to identify new haemozoin-inhibiting chemotherapeutic alternatives for malaria that proved to be useful in different ways when taking into consideration their strengths and limitations.

scholarly journals Causal network models of SARS-CoV-2 expression and aging to identify candidates for drug repurposing

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Anastasiya Belyaeva ◽  
Louis Cammarata ◽  
Adityanarayanan Radhakrishnan ◽  
Chandler Squires ◽  
Karren Dai Yang ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Tyrosine Kinases ◽  
Large Scale ◽  
Drug Repurposing ◽  
Network Models ◽  
Structural Data ◽  
Multiple Data ◽  
Approved Drugs ◽  
Causal Framework

AbstractGiven the severity of the SARS-CoV-2 pandemic, a major challenge is to rapidly repurpose existing approved drugs for clinical interventions. While a number of data-driven and experimental approaches have been suggested in the context of drug repurposing, a platform that systematically integrates available transcriptomic, proteomic and structural data is missing. More importantly, given that SARS-CoV-2 pathogenicity is highly age-dependent, it is critical to integrate aging signatures into drug discovery platforms. We here take advantage of large-scale transcriptional drug screens combined with RNA-seq data of the lung epithelium with SARS-CoV-2 infection as well as the aging lung. To identify robust druggable protein targets, we propose a principled causal framework that makes use of multiple data modalities. Our analysis highlights the importance of serine/threonine and tyrosine kinases as potential targets that intersect the SARS-CoV-2 and aging pathways. By integrating transcriptomic, proteomic and structural data that is available for many diseases, our drug discovery platform is broadly applicable. Rigorous in vitro experiments as well as clinical trials are needed to validate the identified candidate drugs.

scholarly journals Universally available herbal teas based on sage and perilla elicit potent antiviral activity against SARS-CoV-2 in vitro

2020 ◽  
Author(s):  
Vu Thuy Khanh Le-Trilling ◽  
Denise Mennerich ◽  
Corinna Schuler ◽  
Yulia Flores-Martinez ◽  
Benjamin Katschinski ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Low Income ◽  
Treatment Options ◽  
Herd Immunity ◽  
Cost Effective ◽  
Efficient Treatment ◽  
Potent Antiviral Activity ◽  
Approved Drugs ◽  
Socioeconomic Crisis

AbstractThe current SARS-CoV-2/COVID-19 pandemic represents an unprecedented medical and socioeconomic crisis. Highly efficient treatment options preventing morbidity and mortality are not broadly available and approved drugs are hardly affordable in developing countries. Even after vaccine approvals, it will take several months until the vaccinated and convalescent individuals establish herd immunity. Meanwhile, non-pharmaceutical interventions and antiviral treatments are indispensable to curb the death toll of the pandemic. To identify cost-effective and ubiquitously available options, we tested common herbs consumed worldwide as herbal teas. We found that aqueous infusions prepared by boiling leaves of the Lamiaceae plants perilla and sage elicit potent antiviral activity against SARS-CoV-2 in human cells. Sustained antiviral activity was evident even when cells were treated for only half an hour, and in therapeutic as well as prophylactic regimens. Given the urgency, such inexpensive and broadly available substances might provide help during the pandemic - especially in low-income regions.

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