Drug Repositioning: New Approaches and Future Prospects for Life-Debilitating Diseases and the COVID-19 Pandemic Outbreak (original) (raw)
Related papers
Drug Repositioning and Covid-19: A Review
Coronaviruses are large family of viruses distributed in birds, humans and other mammals primarily associated with mild to moderate upper respiratory illnesses. The World Health Organization (WHO) named the novel coronavirus disease as Covid-19 after an outbreak of the disease in Wuhan, Hubei province (China). Over 80 clinical trials including drug repositioning have been initiated to get Covid-19 treatment as captured in ClinicalTrials.gov database. The use of drugs in the treatment of various diseases in human and animal medicine has been facing a great deal of setback primarily due to antibiotic resistance, drug tolerance, emerging infectious diseases and drug adverse effects. This necessitates the need for research into getting new drugs or repositioning the existing ones to meet up with the treatment of both infectious and non-infectious diseases affecting humanity. Drug repositioning is the process of finding new indications and therapeutic targets for already known drugs while developing a new molecular entity (drug) is a long, risky, and overly complex processes with extremely high investment and small expectation of success. Drug discovery has only recorded an average success of about 2.01% despite billions of dollars spent on Research and Development (R&D). Drug repositioning takes an average of 3-12 years to be completed while drug discovery takes an average of 10-17 years to be completed and this is because the initial six to nine years required for the development of new drugs is not necessary in repositioning because the research process goes directly to preclinical testing and clinical trials, thus reducing time, risk, and costs. Also, in drug repositioning a range of pharmacological and toxicological information is already available at the beginning process, as drug candidates to be repositioned have undergone developmental processes such as structural optimization, preclinical and clinical trials. Based on statistics, a reasonable number of drugs and vaccines have been successfully repositioned giving them new indications and formulations which consisted of about 30% of all sold drugs in the year 2009 while only one out of one million potential drug candidates have the possibility of entry into clinical studies with a tendency of having a significant number of failures. Hence the urgent need to discover new uses of existing drugs especially with the emergence of human and animal diseases and the high incidence of drug tolerance and resistance. Drug repositioning is therefore considered as an alternative way as it entails the discovery of new therapeutic indications for already existing drugs.
Drug Repositioning in Response to COVID-19 and other Challenging Diseases
American Journal of Pharmacology and Toxicology, 2022
Coronavirus disease is a highly contagious infection that is majorly associated with upper respiratory tract illnesses. The World Health Organization (WHO) label the novel coronavirus disease COVID-19 after an epidemic of the disease in Wuhan, Hubei province (China). Over 90 clinical trials, including drug repositioning, have been initiated to get COVID-19 treatment/management. Antibiotic resistance, drug tolerance, mutation, and adverse drug effects possess a lot of setbacks during therapy, especially with emerging infectious diseases. This necessitates the need for research into getting newer drugs or repositioning the available ones to meet up with the treatment of both infectious and non-infectious diseases affecting humanity. Drug repositioning is a stepwise process that aids in discovering new indications and therapeutic targets of drugs and it usually takes 3-12 years on average to be completed whereas, in drug discovery, an average of 10-17 years is needed for the whole process. This is because, in repositioning, the research process goes straight to preclinical and clinical trials since both the toxicological and pharmacological profiles of the drug to be repositioned are known, thus reducing time, risk, and costs. Based on 2009 statistics, 30% of all drugs sold in that year are products of repositioning while only one out of one million potential drug candidates have the possibility of entry into clinical studies with a tendency of significant failures. Hence the need to discover additional uses for already established drugs, especially with the emergence of COVID-19. Drug repositioning is therefore considered an alternative way to new drug development as it entails the discovery of newer therapeutic uses of established drugs.
Drug repositioning: Achievements, advancements and barriers
IP innovative publication pvt. ltd, 2019
The humongous cost and long-time duration of new drug development surpasses the rewards in form benefit to patients and cost recovered by the pharmaceutical firms. The problem which this situation gives rise to are productivity gap, pressure by sky soaring prices, incompetency with respect to beneficial generics and issues from regulatory authorities. One advanced approach of drug development which shows potential to tackle these issues is what we refer to as drug repositioning. Drug repurposing is an economical option, time duration to bring a new drug to the market is lesser. There are different approaches to drug repositioning including two broad categories – data driven (computational approaches) and experimental approach. Data driven approaches include - signature matching, molecular docking, genetic mapping, pathway mapping, retrospective clinical analysis, novel data sources while the experimental approach include assays defining target drug interactions, phenotypic screening. Drug repositioning is associated with challenges like chances of failure, regulatory barriers, patency issues and lack of financial incentives. For maximizing the drug repositioning process and to increase its productivity challenges posed to drug repositioning need to be addressed. Keywords: Drug repositioning, Computational approach, Experimental approach.
Orphan/rare drug discovery through drug repositioning
Drug Discovery Today: Therapeutic Strategies, 2011
There are many, often life-threatening, rare/orphan diseases for which there are few or no therapeutic options. They individually affect few people, but collectively impose very high social and economic burdens. New approaches are bringing big pharma resources to solving the problem through drug repositioning of approved drugs. Advances are being spurred by public and private partnerships, government incentives and awareness brought by patient support groups. Scientific discoveries and new technologies are creating many opportunities for drug repositioning.
Repositioning of 8565 Existing Drugs for COVID-19
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 7.1 million people and led to over 0.4 million deaths. Currently, there is no specific anti-SARS-CoV-2 medication. New drug discovery typically takes more than 10 years. Drug repositioning becomes one of the most feasible approaches for combating COVID-19. This work curates the largest available experimental data set for SARS-CoV-2 or SARS-CoV 3CL (main) protease inhibitors. On the basis of this data set, we develop validated machine learning models with relatively low root-mean-square error to screen 1553 FDA-approved drugs as well as another 7012 investigational or off-market drugs in DrugBank. We found that many existing drugs might be potentially potent to SARS-CoV-2. The druggability of many potent SARS-CoV-2 3CL protease inhibitors is analyzed. This work offers a foundation for further experimental studies of COVID-19 drug repositioning. S evere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared in Wuhan, China, in late December 2019 and has rapidly spread around the world. By June 11, 2020, over 7.1 million individuals were infected, and more than 408 000 fatalities had been reported. Currently, there is no specific antiviral drug for this epidemic. It is worth noting that recently, an experimental drug, Remdesivir, has been recognized as a promising anti-SARS-CoV-2 drug. However, the high experimental value of IC 50 (11.41 μM) 1 indicates that it must be used in a large dose in treating COVID-19, which is subject to side effects. Considering the severity of this widespread dissemination and health threats, panicked patients misled by media flocked to pharmacies for Chinese medicine herbs, which were reported to "inhibit" SARS-CoV-2, despite no clinical evidence supporting the claim. Although there is also no evidence for Chloroquine's claimed curing effect, some desperate people take it as "prophylactic" for COVID-19. Many researchers are engaged in developing anti-SARS-CoV-2 drugs. 2,3 However, new drug discovery is a long, costly, and rigorous scientific process. A more effective approach is to search for anti-SARS-CoV-2 therapies from existing drug databases. Drug repositioning (also known as drug repurposing), which concerns the investigation of existing drugs for new therapeutic target indications, has emerged as a successful strategy for drug discovery because of the reduced costs and expedited approval procedures. 4−6 Several successful examples reveal its great value in practice: Nelfinavir, initially developed to treat the human immunodeficiency virus (HIV), is now being used for cancer treatments. Amantadine was first designed to treat the influenza caused by type A influenza viral infection and is being used for the Parkinson's disease. 7 In recent years, the rapid growth of drug-related data sets, as well as open data initiatives, has led to new developments for computational drug repositioning, particularly structural-based drug repositioning (SBDR). Machine learning, network analysis, and text mining and semantic inference are three major computational approaches commonly applied in drug repositioning. 8 The rapid accumulation of genetic and structural databases (https://www.rcsb.org/ and https://www.ncbi.nlm.nih.gov/ genbank/), the development of low-dimensional mathematical representations of complex biomolecular structures, 9 and the availability of advanced deep learning algorithms have made machine learning-based drug repositioning a promising
Repositioning of Drugs as a Promising Strategy to Fight COVID-19
Coronaviruses, 2021
Background and Objective: With the initial case of corona reported in Wuhan, China on 31st December 2020, there has been an unprecedented rise in the coronavirus disease (COVID-19), with over 200 countries all across the world in less than 3 months. By the October 2020, about 40 million population of the world got infected and over one million deaths occurred. Since no WHO and FDA approved medications or vaccines for COVID-19 were available, there was an impatient bustling need to develop a drug for the treatment. Drug repurposing emerged as the easiest and fast emerging strategy to get medicine for COVID-19 with rapid approvals for the clinical trials. The purpose of this study was to evaluate the status of drug repurposing under the clinical and its impact on the development of medicine for COVID-19. Methodology: The study was undertaken to review various clinical trials from the website. www.clinicaltrials.gov . We evaluated 220 ongoing clinical trials with the strategy of ‘drug ...
Repurposing of Drugs for COVID-19: THE WAY FORWARD
Drug repurposing/ repositioning is an unconventional drug discovery approach to explore new therapeutic benefits of existing drugs and many abandoned compounds. It helps to accelerate the drug discovery process through the identification of a novel clinical use for an existing drug. The repositioning or "repurposing" of existing therapies for alternative disease indications is an attractive approach that can save significant investments of time and money during drug development. With the rise in COVID-19 cases globally, the scientific community made enormous efforts in order to rapidly develop vaccines that prevent the spread of COVID-19 infection. Due to the urgent need for development of drugs, repurposing of drugs was one of the most important strategies for COVID-19.
In silico repositioning of approved drugs for rare and neglected diseases
Drug Discovery Today, 2011
Neglected and rare diseases traditionally have not been the focus of large pharmaceutical company research as biotech and academia have primarily been involved in drug discovery efforts for such diseases. This area certainly represents a new opportunity as the pharmaceutical industry investigates new markets. One approach to speed up drug discovery is to examine new uses for existing approved drugs; this is termed drug repositioning or drug repurposing and has become increasingly popular in recent years. Analysis of the literature reveals that using high-throughput screening there have been many examples of FDA approved drugs found to be active against additional targets that can be used to therapeutic advantage for repositioning for other diseases. To date there are far fewer such examples where in silico approaches have allowed for the derivation of new uses. It is suggested that with current technologies and databases of chemical compounds (drugs) and related data, as well as close integration with in vitro screening data, improved opportunities for drug repurposing will emerge. In this publication a review of the literature will highlight several proof of principle examples from areas such as finding new inhibitors for drug transporters with 3D pharmacophores and uncovering molecules active against Mycobacterium tuberculosis (Mtb) using Bayesian models of compound libraries. Research into neglected or rare/orphan diseases can likely benefit from in silico drug repositioning approaches and accelerate drug discovery for these diseases.
Briefings in bioinformatics, 2017
Increase in global population and growing disease burden due to the emergence of infectious diseases (Zika virus), multidrug-resistant pathogens, drug-resistant cancers (cisplatin-resistant ovarian cancer) and chronic diseases (arterial hypertension) necessitate effective therapies to improve health outcomes. However, the rapid increase in drug development cost demands innovative and sustainable drug discovery approaches. Drug repositioning, the discovery of new or improved therapies by reevaluation of approved or investigational compounds, solves a significant gap in the public health setting and improves the productivity of drug development. As the number of drug repurposing investigations increases, a new opportunity has emerged to understand factors driving drug repositioning through systematic analyses of drugs, drug targets and associated disease indications. However, such analyses have so far been hampered by the lack of a centralized knowledgebase, benchmarking data sets and...