Drug Repurposing in Dermatology: Molecular Biology and Omics Approach

2020 ◽  
Author(s):  
Farid A. Badria ◽  
Abdullah A. Elgazar
Keyword(s):  
Clinical Trials ◽  
Drug Discovery ◽  
Molecular Biology ◽  
Adverse Effects ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Pharmaceutical Companies ◽  
Dermatological Condition ◽  
The World ◽  
Initial Discovery

The withdrawal of several blockbuster drugs due to severe adverse effects and the failure of several developed drugs in clinical trials raised questions about the efficacy of current approaches of drug discovery. Moreover, the limitation of resources and the long and costive process of drug discovery made a lot of pharmaceutical companies to employ drug repurposing strategies to get new insights about activities that were not considered during their initial discovery. The development of therapeutics for treatment of dermatological condition is not considered as priority although it affects the lifestyle of thousands of people around the world. Serendipity and observations have contributed significantly in this field but immerse efforts have been exerted to find systematic methods to identify new indications for drugs, especially with the unprecedented progress in molecular biology and omics. So, in this chapter, we will emphasize on different approaches used for drug repositioning and how it was applied to find new therapeutics for different dermatoses.

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.

COVID-19: Are Experimental Drugs Cure or Ill?

2021 ◽  
Vol 16 ◽  
Author(s):  
Bensu Karahalil ◽  
Aylin Elkama
Keyword(s):  
Clinical Trials ◽  
Severe Acute Respiratory Syndrome ◽  
Adverse Effects ◽  
Antiviral Treatment ◽  
Herd Immunity ◽  
Mortality Rates ◽  
Death Rates ◽  
Experimental Drugs ◽  
Combined Use ◽  
The World

Background: Coronavirus disease 2019 (COVID-19) is a new strain of coronavirus. It is characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has quickly influenced all over the world since it spreads easily. Common symptoms are fever, cough, difficulty in breathing and muscle aches. Despite the urgent need to find an effective antiviral treatment, already available agents are being used alone or in combination all over the world. At the beginning of the pandemic, death rates of infection caused by COVID-19 are high but "is COVID-19 responsible for all deaths?", or “are there any contributions of the frequently used drugs in this period to these deaths?” Surely herd immunity plays a major role and has the contribution in the decline in mortality rates. Meanwhile, it is kept in mind that due to safety concerns, changes have also been made to the dosage and combined use of frequently used drugs. Objective: In this review, answers to two questions above and the safety of treatments, toxicities of agents involving chloroquine, hydroxychloroquine, remdesivir, favipiravir, lopiravir/ritonavir, sarilumab, tocilizumab, siltuximab, corticosteroids and bromhexine which are the most frequently used in both Turkey and all over the world will be summarized. Conclusion: Among these drugs favipiravir seems the most promising drug due to more tolerable adverse effects. More clinical trials with large sample sizes are needed to find the most effective and safe drug for COVID-19 treatment.

scholarly journals Using systems medicine to identify a therapeutic agent with potential for repurposing in inflammatory bowel disease

2020 ◽  
Vol 13 (11) ◽  
pp. dmm044040 ◽  
Author(s):  
Katie Lloyd ◽  
Stamatia Papoutsopoulou ◽  
Emily Smith ◽  
Philip Stegmaier ◽  
Francois Bergey ◽  
...  
Keyword(s):  
Drug Discovery ◽  
In Silico ◽  
Nuclear Translocation ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Peritoneal Macrophages ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Aseptic Conditions ◽  
Novel Drug

ABSTRACTInflammatory bowel diseases (IBDs) cause significant morbidity and mortality. Aberrant NF-κB signalling is strongly associated with these conditions, and several established drugs influence the NF-κB signalling network to exert their effect. This study aimed to identify drugs that alter NF-κB signalling and could be repositioned for use in IBD. The SysmedIBD Consortium established a novel drug-repurposing pipeline based on a combination of in silico drug discovery and biological assays targeted at demonstrating an impact on NF-κB signalling, and a murine model of IBD. The drug discovery algorithm identified several drugs already established in IBD, including corticosteroids. The highest-ranked drug was the macrolide antibiotic clarithromycin, which has previously been reported to have anti-inflammatory effects in aseptic conditions. The effects of clarithromycin effects were validated in several experiments: it influenced NF-κB-mediated transcription in murine peritoneal macrophages and intestinal enteroids; it suppressed NF-κB protein shuttling in murine reporter enteroids; it suppressed NF-κB (p65) DNA binding in the small intestine of mice exposed to lipopolysaccharide; and it reduced the severity of dextran sulphate sodium-induced colitis in C57BL/6 mice. Clarithromycin also suppressed NF-κB (p65) nuclear translocation in human intestinal enteroids. These findings demonstrate that in silico drug repositioning algorithms can viably be allied to laboratory validation assays in the context of IBD, and that further clinical assessment of clarithromycin in the management of IBD is required.This article has an associated First Person interview with the joint first authors of the paper.

scholarly journals Shotgun Drug Repurposing Biotechnology to Tackle Epidemics and Pandemics

2020 ◽  
Author(s):  
William Mangione ◽  
Zackary Falls ◽  
Thomas Melendy ◽  
Gaurav Chopra ◽  
Ram Samudrala
Keyword(s):  
Clinical Trials ◽  
Drug Discovery ◽  
Computational Analysis ◽  
Drug Repurposing ◽  
The Future ◽  
Respiratory Coronavirus ◽  
Novel Drug

In this manuscript we highlight consensus between the list of drugs currently in clinical trials to treat COVID-19, the worldwide pandemic caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), and the list of predictions made using our shotgun drug discovery, repurposing, and design platform known as CANDO (Computational Analysis of Novel Drug Opportunities). We make the argument that increased funding and development for drug repurposing biotechnology like ours will help combat the inevitable pathogenic outbreaks of the future. <br>

scholarly journals Role of Regulatory Authorities on the Working of Contract Research Organization and Pharmaceutical Company’s Clinical Trials in India

2021 ◽  
Vol 16 (3) ◽  
pp. 87-91
Author(s):  
Poonam Chauhan ◽  
Monica Mendonca
Keyword(s):  
Clinical Trials ◽  
Drug Discovery ◽  
Clinical Research ◽  
Vital Role ◽  
Research Organization ◽  
Pharmaceutical Companies ◽  
Contract Research Organization ◽  
Contract Research ◽  
Target Disease ◽  
The Masses

The evolution of the drug development process and testing its efficacy is a primary responsibility of pharmaceutical companies. The time cost investment involved in identifying a compound suitable to its target disease and making it available to the masses eventually led to the rise of the Contract Research Organization (CRO) in the domain of clinical research.  Pharmaceutical companies outsource the research and clinical trials to CRO’s. A CRO has a vital role from drug discovery to the launch and marketing of drugs. India is emerging as attractive location for global clinical trial. It has cost advantage compared to other countries and a well-developed associated services like data management, medical writing and pharmacovigilance.  The Central Drug Standard Control Organization (CDSCO) is the National Regulatory Authority in India that aims to bring safe drugs and standardize clinical research. Pharmaceutical Companies benefit by strategically working with CRO to gain speed and efficiency in drug discovery, generation and retention of clinical data integrity. The risk associated with CRO relates to delays and inferior quality of work, thereby making CRO a critical decision for Pharmaceutical Company.

scholarly journals Using systems medicine to identify a therapeutic agent with potential for repurposing in Inflammatory Bowel Disease

2019 ◽  
Author(s):  
Katie Lloyd ◽  
Stamatia Papoutsopoulou ◽  
Emily Smith ◽  
Philip Stegmaier ◽  
Francois Bergey ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Drug Discovery ◽  
Bowel Disease ◽  
In Silico ◽  
Nuclear Translocation ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Peritoneal Macrophages ◽  
Inflammatory Bowel ◽  
Aseptic Conditions

AbstractObjectiveInflammatory bowel diseases cause significant morbidity and mortality. Aberrant NF-κB signalling is strongly associated with these conditions, and several established drugs influence the NF-κB signalling network to exert their effect. This study aimed to identify drugs which alter NF-κB signalling and may be repositioned for use in inflammatory bowel disease.DesignThe SysmedIBD consortium established a novel drug-repurposing pipeline based on a combination of in-silico drug discovery and biological assays targeted at demonstrating an impact on NF-kappaB signalling, and a murine model of IBD.ResultsThe drug discovery algorithm identified several drugs already established in IBD, including corticosteroids. The highest-ranked drug was the macrolide antibiotic Clarithromycin, which has previously been reported to have anti-inflammatory effects in aseptic conditions.Clarithromycin’s effects were validated in several experiments: it influenced NF-κB mediated transcription in murine peritoneal macrophages and intestinal enteroids; it suppressed NF-κB protein shuttling in murine reporter enteroids; it suppressed NF-κB (p65) DNA binding in the small intestine of mice exposed to LPS, and it reduced the severity of dextran sulphate sodium-induced colitis in C57BL/6 mice. Clarithromycin also suppressed NF-κB (p65) nuclear translocation in human intestinal enteroids.ConclusionsThese findings demonstrate that in-silico drug repositioning algorithms can viably be allied to laboratory validation assays in the context of inflammatory bowel disease; and that further clinical assessment of clarithromycin in the management of inflammatory bowel disease is required.

scholarly journals The Stages of Drug Discovery and Development Process

2019 ◽  
Vol 7 (6) ◽  
pp. 62-67 ◽  
Author(s):  
Amol B Deore ◽  
Jayprabha R Dhumane ◽  
Rushikesh Wagh ◽  
Rushikesh Sonawane
Keyword(s):  
Clinical Trials ◽  
Drug Discovery ◽  
Drug Development ◽  
Development Process ◽  
Regulatory Requirements ◽  
Drug Discovery And Development ◽  
Biological Targets ◽  
New Drug ◽  
Initial Discovery ◽  
New Research

Drug discovery is a process which aims at identifying a compound therapeutically useful in curing and treating disease. This process involves the identification of candidates, synthesis, characterization, validation, optimization, screening and assays for therapeutic efficacy. Once a compound has shown its significance in these investigations, it will initiate the process of drug development earlier to clinical trials. New drug development process must continue through several stages in order to make a medicine that is safe, effective, and has approved all regulatory requirements. One overall theme of our article is that the process is sufficiently long, complex, and expensive so that many biological targets must be considered for every new medicine ultimately approved for clinical use and new research tools may be needed to investigate each new target.  From initial discovery to a marketable medicine is a long, challenging task. It takes about 12 - 15 years from discovery to the approved medicine and requires an investment of about US $1 billion. On an average, a million molecules screened but only a single is explored in late stage clinical trials and is finally made obtainable for patients. This article provides a brief outline of the processes of new drug discovery and development.   

scholarly journals COVID-19 Vaccines in Pakistan: Efficacy, Adverse Effects and Availability

2021 ◽  
Vol 10 (2) ◽  
pp. 125-130
Author(s):  
Soma Siddique ◽  
Shaheer Ahmed
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Adverse Effects ◽  
Mode Of Action ◽  
Public Awareness ◽  
Grey Literature ◽  
Large Population ◽  
Review Article ◽  
Pain On Injection ◽  
The World

In this review article, we aim to document the efficacy, adverse effects, mode of action, required doses, and availability of the major vaccines available in Pakistan till 20 May 2021. We reviewed all available literature on COVID-19 vaccines in PubMed and Google scholar. We also reviewed articles from grey literature. Currently, Pfizer–BioNTech and Moderna, Sinopharm (China), Sputnik V (Russia), CoronaVac (popularly known as Sinovac) (China), Cansino, and Vaxzevria vaccines have been authorized for emergency use in several countries. Pakistan has sanctioned the use of all the aforementioned vaccines except Pfizer and Moderna. As per their efficacy, Pfizer and Moderna have been found most effective among all the vaccines with 95% effectiveness, while the Vaxzevria, Sputnik V, Sinopharm, and Cansino have shown 70%, 91.6%, 79.34%, and 90% effectiveness, respectively. All the vaccines have shown milder side effects like headache, fever, and pain on injection sites. To curb the pandemic, more clinical trials are being conducted throughout the world. Importantly public awareness is warranted to achieve the target of vaccinating a large population.

scholarly journals Analysis of Vaccines to tackle COVID-19 with Patent Review

2020 ◽  
Author(s):  
Divyansh Sehgal
Keyword(s):  
Infectious Disease ◽  
Clinical Trials ◽  
Pharmaceutical Companies ◽  
The Novel ◽  
Development Activity ◽  
Stage Of Development ◽  
Patent Review ◽  
The World ◽  
Novel Coronavirus ◽  
Current Stage

As humans are spreading throughout the world, infectious diseases have been a constant companion such as Bubonic Plague (200 Million deaths), 17th Century Great Plague (3 Million deaths), Plague of Justinian (30-50 Million deaths), etc . Coronavirus Disease (COVID-19) which was published on 11th January 2020 showing the intensity of Global research and development activity to develop a drug/vaccine against the disease. COVID-19 is an infectious disease caused by a newly discovered coronavirus. Human to human transmission has created a pandemic situation across the world. Pharmaceutical companies play a crucial role in this scenario to provide Drugs/Vaccines/Therapies to treat and tackle the novel coronavirus disease of 2019. This paper consists of the Drugs and Vaccines which are developed, or in the process of development , their current stage of development (clinical trials) with their patent review.

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