Drug repurposing approach to combating coronavirus: Potential drugs and drug targets.
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ABSTRACT:
SUBMITTER: Xu J
PROVIDER: S-EPMC8044022 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
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Project description:The present pandemic of SARS-CoV-2 has been a tough task for the whole world to deal with. With the absence of specific drugs or vaccines against SARS-CoV-2, the situation is very difficult to control. Apart from the absence of specific therapies, the lack of knowledge about potential therapeutic targets and individual perception is adding to the complications. The present review describes the novel SARS-CoV-2 structure, surface proteins, asymptomatic and symptomatic transmission in addition to the genotype and phenotype of SARS-CoV-2 along with genetic strains and similarity between SARS, MERS and SARS-CoV-2. Therapeutic strategies such as inhibition of the endocytic pathway and suppressing RNA polymerase activity by metal ions, which could be quite beneficial for controlling COVID-19, are outlined. The drug repurposing for SARS-CoV-2 is discussed in detail along with therapeutic classes such as antivirals, antibiotics, and amino quinolones and their probable role in suppressing SARS-CoV-2 with reference to case studies. The ongoing clinical trials both with respect to drug repurposing and vaccines are summarized along with a brief description. The recent advancements and future perspective of ongoing research for therapy and detection of SARS-CoV-2 are provided. The review, in brief, summarizes epidemiology, therapy and the current scenario for combating SARS-CoV-2.
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Project description:Repurposing regulatory agency approved drugs and investigational compounds with known safety profiles can significantly fast track the drug development timeline over de novo drug discovery, with lower investment requirements and improved attrition rate. These advantages are vital in any epidemic or pandemic situation, where hospital beds are occupied by patients for whom there is no known treatment. Here we examine drug repurposing in the context of human coronaviruses, SARS-CoV, MERS-CoV, and, in particular, SARS-CoV-2, the virus currently causing a continued widespread pandemic with substantial impacts on public health and economy. The key druggable targets explored were those involved in viral entry, viral replication, and viral-induced ARDS, as well as viral proteases, with a focus on the strategy by which the drugs were repurposed.
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Project description:As of April 9, 2020, a novel coronavirus (SARS-CoV-2) had caused 89,931 deaths and 1,503,900 confirmed cases worldwide, which indicates an increasingly severe and uncontrollable situation. Initially, little was known about the virus. As research continues, we now know the genome structure, epidemiological and clinical characteristics, and pathogenic mechanisms of SARS-CoV-2. Based on this knowledge, potential targets involved in the processes of virus pathogenesis need to be identified, and the discovery or development of drugs based on these potential targets is the most pressing need. Here, we have summarized the potential therapeutic targets involved in virus pathogenesis and discuss the advances, possibilities, and significance of drugs based on these targets for treating SARS-CoV-2. This review will facilitate the identification of potential targets and provide clues for drug development that can be translated into clinical applications for combating SARS-CoV-2.
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Project description:Development of novel antiviral molecules from the beginning costs an average of $350 million to $2 billion per drug, and the journey from the laboratory to the clinic takes about 10-15 years. Utilization of drug repurposing approaches has generated substantial interest in order to overcome these drawbacks. A drastic reduction in the failure rate, which otherwise is ~92%, is achieved with the drug repurposing approach. The recent exploration of the drug repurposing approach to combat the COVID-19 pandemic has further validated the fact that it is more beneficial to reinvestigate the in-practice drugs for a new application instead of designing novel drugs. The first successful example of drug repurposing is zidovudine (AZT), which was developed as an anti-cancer agent in the 1960s and was later approved by the US FDA as an anti-HIV therapeutic drug in the late 1980s after fast track clinical trials. Since that time, the drug repurposing approach has been successfully utilized to develop effective therapeutic strategies against a plethora of diseases. Hence, an extensive application of the drug repurposing approach will not only help to fight the current pandemics more efficiently but also predict and prepare for newly emerging viral infections. In this review, we discuss in detail the drug repurposing approach and its advancements related to viral infections such as Human Immunodeficiency Virus (HIV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).
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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
Project description:Drug repurposing is also termed as drug repositioning or therapeutic switching. This method is applied to identify the novel therapeutic agents from the existing FDA approved clinically used drug molecules. It is considered as an efficient approach to develop drug candidates with new pharmacological activities or therapeutic properties. As the drug discovery is a costly, time-consuming, laborious, and highly risk process, the novel approach of drug repositioning is employed to increases the success rate of drug development. This strategy is more advantageous over traditional drug discovery process in terms of reducing duration of drug development, low-cost, highly efficient and minimum risk of failure. In addition to this, World health organization declared Coronavirus disease (COVID-19) as pandemic globally on February 11, 2020. Currently, there is an urgent need to develop suitable therapeutic agents for the prevention of the outbreak of COVID-19. So, various investigations were carried out to design novel drug molecules by utilizing different approaches of drug repurposing to identify drug substances for treatment of COVID-19, which can act as significant inhibitors against viral proteins. It has been reported that COVID-19 can infect human respiratory system by entering into the alveoli of lung via respiratory tract. So, the infection occurs due to specific interaction or binding of spike protein with angiotensin converting enzyme-2 (ACE-2) receptor. Hence, drug repurposing strategy is utilized to identify suitable drugs by virtual screening of drug libraries. This approach helps to determine the binding interaction of drug candidates with target protein of coronavirus by using computational tools such as molecular similarity and homology modeling etc. For predicting the drug-receptor interactions and binding affinity, molecular docking study and binding free energy calculations are also performed. The methodologies involved in drug repurposing can be categorized into three groups such as drug-oriented, target-oriented and disease or therapy-oriented depending on the information available related to quality and quantity of the physico-chemical, biological, pharmacological, toxicological and pharmacokinetic property of drug molecules. This review focuses on drug repurposing strategy applied for existing drugs including Remdesivir, Favipiravir, Ribavirin, Baraticinib, Tocilizumab, Chloroquine, Hydroxychloroquine, Prulifloxacin, Carfilzomib, Bictegravir, Nelfinavir, Tegobuvir and Glucocorticoids etc to determine their effectiveness toward the treatment of COVID-19.
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