Drug repositioning for dengue haemorrhagic fever by integrating multiple omics analyses

Amemiya, Takayuki; Gromiha, M. Michael; Horimoto, Katsuhisa; Fukui, Kazuhiko

doi:10.1038/s41598-018-36636-1

Cited by 27 publications

(29 citation statements)

References 60 publications

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“…Healthy). [22] Similar to all bioinformatics pipelines, parameter and algorithm selection impact results, and may not be optimal even after tuning, which makes use of a black-box approach for drug repositioning less appealing.…”

mentioning

confidence: 99%

Drug Repositioning Suggests a Role for the Heat Shock Protein 90 Inhibitor Geldanamycin in Treating COVID-19 Infection

Sultan¹,

Howard²,

Tbakhi³

2020

Preprint

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Drug repositioning offers an unmatched opportunity to offer novel therapeutics to treat SARS family of coronaviruses (SARS-FCoVs); an issue that became extremely urgent with the spreading of a novel virus with potential to threaten the lives of millions of people. Hereby, we analyzed a dataset of patients who presented with SARS during the 2003 outbreak. We established a gene signature that defines differential gene expression in patients who were sick with SARS vs. healthy controls and convalescent patients. We used a robust platform to conduct drug repositioning based on clustered gene expression and pathway enrichment to identify best matching drugs. We identified 55 agents of potential benefit. In most of these drugs we were able to establish a link to previous related research, use as antiviral, or at least a hypothetical role in treating SARS-FCoVs. Most notably, the heat shock protein 90 (hsp90) emerged as a major component that enables viruses to hijack infected cells through the process of autophagy. Almost half of the drugs identified could be linked to hsp90. As such, we propose using hsp90 inhibitors, mainly geldanamycin and its derivatives, to treat COVID-19.

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mentioning

confidence: 99%

Drug Repositioning Suggests a Role for the Heat Shock Protein 90 Inhibitor Geldanamycin in Treating COVID-19 Infection

Sultan¹,

Howard²,

Tbakhi³

2020

Preprint

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“…Also, multiple omics analysis mapped to significant pathways allows for the simultaneous detection of target genes and human proteins for their potential in specific diseases. For instance, drug candidates and human protein targets have been identified for several diseases such as dengue haemorrhagic fever [27], head and neck squamous cell carcinoma [28] and rheumatoid arthritis [29] amongst many others, using this approach. However, there are also downsides to this approach.…”

Section: Pathway Mappingmentioning

confidence: 99%

Drug Repositioning: New Approaches and Future Prospects for Life-Debilitating Diseases and the COVID-19 Pandemic Outbreak

Low

Farouk

Lal

2020

Viruses

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Traditionally, drug discovery utilises a de novo design approach, which requires high cost and many years of drug development before it reaches the market. Novel drug development does not always account for orphan diseases, which have low demand and hence low-profit margins for drug developers. Recently, drug repositioning has gained recognition as an alternative approach that explores new avenues for pre-existing commercially approved or rejected drugs to treat diseases aside from the intended ones. Drug repositioning results in lower overall developmental expenses and risk assessments, as the efficacy and safety of the original drug have already been well accessed and approved by regulatory authorities. The greatest advantage of drug repositioning is that it breathes new life into the novel, rare, orphan, and resistant diseases, such as Cushing’s syndrome, HIV infection, and pandemic outbreaks such as COVID-19. Repositioning existing drugs such as Hydroxychloroquine, Remdesivir, Ivermectin and Baricitinib shows good potential for COVID-19 treatment. This can crucially aid in resolving outbreaks in urgent times of need. This review discusses the past success in drug repositioning, the current technological advancement in the field, drug repositioning for personalised medicine and the ongoing research on newly emerging drugs under consideration for the COVID-19 treatment.

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“…To identify novel and potent drug candidates, approved drugs such as lovastatin (31), chloroquine (39), prednisolone (51), balapiravir (52), and celgosivir (53) were investigated for the proof-off concept clinical trials for dengue viral infection ( Figure 5). Although the results showed that they were safe in patients with acute dengue, drugs failed to meet prior-defined trial endpoints [112][113][114][115][116]. Besides, two clinical trials conducted in Thailand and Singapore involving ivermectin (54) and ketotifen (55), the preliminary result was quite promising as phase 2 study of the drug 54 suggested a reduction in serum NS1 levels and body temperature [117].…”

Section: Figure 3 Chemical Structures Of Drugs Repurposed For Cancermentioning

confidence: 99%

A medicinal chemistry perspective of drug repositioning: Recent advances and challenges in drug discovery

Pillaiyar

Meenakshisundaram²,

Manickam

et al. 2020

European Journal of Medicinal Chemistry

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Drug repurposing is a strategy consisting of finding new indications for already known marketed drugs used in various clinical settings or highly characterized compounds despite they can be failed drugs. Recently, it emerges as an alternative approach for the rapid identification and development of new pharmaceuticals for various rare and complex diseases for which lack the effective drug treatments. The success rate of drugs repurposing approach accounts for approximately 30% of new FDA approved drugs and vaccines in recent years.This review focuses on the status of drugs repurposing approach for various diseases including skin diseases, infective, inflammatory, cancer, and neurodegenerative diseases.Efforts have been made to provide structural features and mode of actions of drugs.Keywords: Cancer, drug repositioning, drug reprofiling, recycling of drugs, drug discovery, inflammation, neurodegenerative diseases, skin diseases. since clinical and pre-clinical studies of the re-purposed candidates are already being documented in the original indication(s). Thus, it reduces the time and cost needed to reach the market and risk intrinsic to any research and development program. Moreover, the risk of clinical failure is also low. As an added advantage, this approach gives a possibility to widen the market and to prolong the application of the patent life of a drug. There are mainly two ways to proceed drug-repositioning approach such as experimental strategies and computational strategies.Experimental repurposing strategies include binding assays and phenotypic screening methods, which can be to find binding interactions of drug molecules to assay components and to identify lead compounds from a vide range of compound libraries, respectively [10].Computational approaches are categorized into target-/mechanism based, knowledge-based, pathway-and network-based approaches. These approaches are proven economic in discovering novel therapeutic ligands. Most notably, computational methods augment the drug discovery process by effectively utilizing cheminformatics, bioinformatics, network biology and systems biology. More specifically, these methods exploit known targets, drugs, disease biomarkers or pathways to establish novel methods and accelerate the planning of crucial clinical trials [11].In this perspective, we focused on the status of drugs repurposing approaches for various diseases including skin diseases, infective, inflammatory, cancer, and neurodegenerative diseases. Efforts have been made to provide structural features, and modes of action of drugs, which are exclusively small molecules, peptidomimetics, and macrocyclic compounds.Antibodies, vaccines, and any other biological drugs are not discussed. Drugs repositioning for skin whitening activity.Melanin is a collection of natural pigments that primarily determine the skin, hair and hair color of the human. Melanocytes, which are found in the basal layer of the epidermis, produce melanin by the process called melanogenesis upon the skin exposure to the ultra...

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Drug repositioning for dengue haemorrhagic fever by integrating multiple omics analyses

Cited by 27 publications

References 60 publications

Drug Repositioning Suggests a Role for the Heat Shock Protein 90 Inhibitor Geldanamycin in Treating COVID-19 Infection

Drug Repositioning Suggests a Role for the Heat Shock Protein 90 Inhibitor Geldanamycin in Treating COVID-19 Infection

Drug Repositioning: New Approaches and Future Prospects for Life-Debilitating Diseases and the COVID-19 Pandemic Outbreak

A medicinal chemistry perspective of drug repositioning: Recent advances and challenges in drug discovery

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