scholarly journals Rational Drug Repurposing: Focus on Lysosomotropism, Targets in Disease Process, Drug Profile, and Pulmonary Tissue Accumulation in SARS-CoV-2 Infection/COVID-19

2020 ◽  
Vol 11 ◽  
Author(s):  
Markus Blaess ◽  
Lars Kaiser ◽  
Oliver Sommerfeld ◽  
Simone Rentschler ◽  
René Csuk ◽  
...  
Keyword(s):  
Disease Process ◽  
Drug Repurposing ◽  
Pulmonary Tissue ◽  
Drug Profile ◽  
Tissue Accumulation ◽  
Rational Drug

scholarly journals NICEdrug.ch, a workflow for rational drug design and systems-level analysis of drug metabolism

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Homa MohammadiPeyhani ◽  
Anush Chiappino-Pepe ◽  
Kiandokht Haddadi ◽  
Jasmin Hafner ◽  
Noushin Hadadi ◽  
...  
Keyword(s):  
Drug Targets ◽  
Drug Repurposing ◽  
Rational Drug Design ◽  
Bioactive Molecules ◽  
Lead Discovery ◽  
Minimal Impact ◽  
Practical Applications ◽  
Rational Drug ◽  
Golden Standard ◽  
And Performance

The discovery of a drug requires over a decade of intensive research and financial investments – and still has a high risk of failure. To reduce this burden, we developed the NICEdrug.ch resource, which incorporates 250,000 bioactive molecules, and studied their enzymatic metabolic targets, fate, and toxicity. NICEdrug.ch includes a unique fingerprint that identifies reactive similarities between drug–drug and drug–metabolite pairs. We validated the application, scope, and performance of NICEdrug.ch over similar methods in the field on golden standard datasets describing drugs and metabolites sharing reactivity, drug toxicities, and drug targets. We use NICEdrug.ch to evaluate inhibition and toxicity by the anticancer drug 5-fluorouracil, and suggest avenues to alleviate its side effects. We propose shikimate 3-phosphate for targeting liver-stage malaria with minimal impact on the human host cell. Finally, NICEdrug.ch suggests over 1300 candidate drugs and food molecules to target COVID-19 and explains their inhibitory mechanism for further experimental screening. The NICEdrug.ch database is accessible online to systematically identify the reactivity of small molecules and druggable enzymes with practical applications in lead discovery and drug repurposing.

scholarly journals Fi-score: a novel approach to characterise protein topology and aid in drug discovery studies

2020 ◽  
Author(s):  
Austė Kanapeckaitė ◽  
Claudia Beaurivage ◽  
Matthew Hancock ◽  
Erik Verschueren
Keyword(s):  
Dihedral Angle ◽  
Target Selection ◽  
Gaussian Mixture Models ◽  
Drug Repurposing ◽  
Gaussian Mixture ◽  
Rational Drug Design ◽  
Drug Candidates ◽  
Novel Approach ◽  
Protein Fingerprinting ◽  
Rational Drug

AbstractTarget evaluation is at the centre of rational drug design and biologics development. In order to successfully engineer antibodies, T-cell receptors or small molecules it is necessary to identify and characterise potential binding or contact sites on therapeutically relevant target proteins. Currently, there are numerous challenges in achieving a better docking precision as well as characterising relevant sites. We devised a first-of-its-kind in silico protein fingerprinting approach based on dihedral angle and B-factor distribution to probe binding sites and sites of structural importance. In addition, we showed that the entire protein regions or individual structural subsets can be profiled using our derived fi-score based on amino acid dihedral angle and B-factor distribution. We further described a method to assess the structural profile and extract information on sites of importance using machine learning Gaussian mixture models. In combination, these biophysical analytical methods could potentially help to classify and systematically analyse not only targets but also drug candidates that bind to specific sites which would greatly improve pre-screening stage, target selection and drug repurposing efforts in finding other matching targets.

scholarly journals Binding site matching in rational drug design: algorithms and applications

2018 ◽  
Vol 20 (6) ◽  
pp. 2167-2184 ◽  
Author(s):  
Misagh Naderi ◽  
Jeffrey Mitchell Lemoine ◽  
Rajiv Gandhi Govindaraj ◽  
Omar Zade Kana ◽  
Wei Pan Feinstein ◽  
...  
Keyword(s):  
Small Molecules ◽  
Binding Site ◽  
Protein Structures ◽  
Chemical Properties ◽  
Drug Repurposing ◽  
Rational Drug Design ◽  
Basic Knowledge ◽  
Rational Drug ◽  
Binding Pockets ◽  
Local Protein

Abstract Interactions between proteins and small molecules are critical for biological functions. These interactions often occur in small cavities within protein structures, known as ligand-binding pockets. Understanding the physicochemical qualities of binding pockets is essential to improve not only our basic knowledge of biological systems, but also drug development procedures. In order to quantify similarities among pockets in terms of their geometries and chemical properties, either bound ligands can be compared to one another or binding sites can be matched directly. Both perspectives routinely take advantage of computational methods including various techniques to represent and compare small molecules as well as local protein structures. In this review, we survey 12 tools widely used to match pockets. These methods are divided into five categories based on the algorithm implemented to construct binding-site alignments. In addition to the comprehensive analysis of their algorithms, test sets and the performance of each method are described. We also discuss general pharmacological applications of computational pocket matching in drug repurposing, polypharmacology and side effects. Reflecting on the importance of these techniques in drug discovery, in the end, we elaborate on the development of more accurate meta-predictors, the incorporation of protein flexibility and the integration of powerful artificial intelligence technologies such as deep learning.

scholarly journals An Uncommon Case of Secondary Organizing Pneumonia Due to Influenza Type B

2021 ◽  
Vol 11 (1) ◽  
pp. 174-177
Author(s):  
Parth Shah ◽  
Philip T. Sobash ◽  
Krishna Vedala ◽  
Krishna Kakkera ◽  
Gilbert-Roy Kamoga
Keyword(s):  
Tissue Injury ◽  
Disease Process ◽  
Successful Outcome ◽  
Influenza B ◽  
Organizing Pneumonia ◽  
Hypoxemic Respiratory Failure ◽  
Acute Hypoxemic Respiratory Failure ◽  
Pulmonary Tissue ◽  
Uncommon Case ◽  
Inflammatory Changes

Secondary organizing pneumonia refers to a disease process caused by pulmonary tissue injury. Various insults can cause secondary organizing pneumonia, including multiple types of infections and cancer. The mainstay of diagnosis is a combination of imaging and lung biopsy showing inflammatory changes, specifically plugs with granulated tissue and fibrosis. Clinical suspicion needs to be raised for secondary organizing pneumonia when a patient is requiring increasing amounts of oxygen in the presence of treatment for pneumonia or another underlying lung disease. Here, we present the case of a 65-year-old male who presented with acute hypoxemic respiratory failure in the setting of previously having been tested positive for influenza B. Aggressive steroids with eventual tapering of his O2 requirements led to a successful outcome. While influenza has been reported as a cause of secondary organizing pneumonia after proceeding infection, these cases are usually represented by type A, rather than B.

scholarly journals Computational Repurposing Model of Curcumin as a Drug

2021 ◽  
Vol 68 (1) ◽  
Author(s):  
Ratna Roy ◽  
Ratul Bhowmik ◽  
Shatarupa Seth ◽  
Snigdha Bhattacharyya ◽  
Sounok Sengupta
Keyword(s):  
Viral Infections ◽  
Drug Repurposing ◽  
Viral Disease ◽  
Global Scale ◽  
Rational Drug Design ◽  
Viral Diseases ◽  
The Novel ◽  
Viral Pathogens ◽  
Positive Effects ◽  
Rational Drug

Viral diseases continue to be a public threat on a global scale day by day and the world is in a continuing battle with the novel deadly viral Diseases and with no prompt medicines accessible the scourge brought about by the disease is expanding step by step. The ongoing need to develop new antiviral drugs with fewer side-effects and that are effective against viral pathogens has spurred the research community to invest in various drug discovery strategies, one of which is drug repurposing the methods of finding most promising existing compounds which has able to give best positive effects against viral infections. We present a docking?based screening using a quantum mechanical scoring of drug Curcumin with Proteins with PDB id’s 4B3V, 5LK0, 6BM8, 4QUZ, 6SJV, 1JLF, 5EG7, 7K40 could display antiviral activity against Rubella, Hanta, Herpes, Noro, papilloma, HIV, Influenza, COVID19. Clearly, these compounds should be further evaluated in experimental assays and clinical trials to confirm their actual activity against the viral disease. We hope that repurposing of the drug from our recommendation may contribute to the rational drug design against the above viruses.

Rational Drug Repurposing Using sscMap Analysis in a HOX-TALE Model of Leukemia

2014 ◽  
pp. 349-370
Author(s):  
Laura M. J. Kettyle ◽  
Fabio G. Liberante ◽  
Alexander Thompson
Keyword(s):  
Drug Repurposing ◽  
Rational Drug

scholarly journals DRUG REPURPOSING FOR MALARIA AND DENGUE USING COMPUTATIONAL MODELLING.

2020 ◽  
Vol 4 (11) ◽  
Author(s):  
Prajakta Velankar ◽  
Sara Rehman ◽  
Yukti Thakkar
Keyword(s):  
Clinical Trials ◽  
Drug Design ◽  
Antiviral Activity ◽  
Computational Modelling ◽  
Drug Repurposing ◽  
Rational Drug Design ◽  
Quantum Mechanical ◽  
Rational Drug ◽  
The World ◽  
Approved Drugs

By and by the world is in a battle with the diseases like Malaria and Dengue with no prompt medicines accessible the scourge brought about by the Malaria and Dengue is expanding step by step. A ton of researchers are continuing for the potential medication up-and-comer that could help the medical care framework in this battle. We present a docking?based screening using a quantum mechanical scoring of a library built from approved drugs ie Remdesivir, Hydroxy-chloroquine, Curcumin, Moroxydine, Artesunate Sulphate, Mefloquine, Doxycycline, Atovaquone, Indinavir, and compounds that are with Malaria and Dengue Mpro Proteins could display antiviral activity against these diseases. Clearly, these compounds should be further evaluated in experimental assays and clinical trials to confirm their actual activity against the disease. We hope that these findings may contribute to the rational drug design against Malaria and Dengue Keywords: Malaria, Dengue, Drug Repurposings, Computer Aid Drug Design, In silico drug development

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