scholarly journals PERSPECTIVE INSIGHT AND APPLICATION OF IN-SILICO TOOL AS VIRTUAL SCREENING METHOD FOR LEAD DESIGNING AND DEVELOPMENT

2021 ◽  
Vol 11 (6) ◽  
pp. 16-24
Author(s):  
Hemant U Chikhale
Keyword(s):  
In Silico ◽  
Screening Method ◽  
Lead Discovery ◽  
Environmental Technology ◽  
Lead Structure ◽  
Drug Candidates ◽  
Underlying Principle ◽  
Novel Drug ◽  
Investigative Process ◽  
Specific Illness

Humans are now in a bioinformatics and chemo informatics century, where we can foresee data across domains like as healthcare, the environmental, technology, and public health. The use of information sharing in silico methodologies has impacted sickness administration by predicting the absorption, distribution, metabolism, excretion, and toxicity (ADMET) patterns of synthetic compounds and efficient and environmentally succeeding pharmaceuticals upfront. The purpose of lead discovery and design is to create the appearance of novel drug candidates that can attach to a specific illness cause. The lead investigative process starts with the recognition of the lead structure, which is followed by the synthesis of its analogs and their estimation in order to produce a candidate for lead improvement. The finding of the proper lead exact is the fundamental and primary worked in the traditional lead discovery progression, and the use of computer (in silico) approaches is widely used in lead innovation. A medicinal chemist's passion for building lead structure is piqued by biomolecules, which are often made up of DNA, RNA, and proteins (such as enzymes, receptors, transporters, and ion channels). The underlying principle of such nuts and bolts is noteworthy to be acquainted with their pharmacological implication to the disease under examination. The motive of this review piece of writing is to emphasize several of the in silico methods that are used in lead discovery and to express the applications of these computational methods.

Integrated in Silico Methods for the Design and Optimization of Novel Drug Candidates

Oncology ◽  
2017 ◽  
pp. 434-481
Author(s):  
Nikola Minovski ◽  
Marjana Novič
Keyword(s):  
In Silico ◽  
Comprehensive Overview ◽  
Design And Optimization ◽  
Drug Candidates ◽  
In Silico Drug Design ◽  
Current Trends ◽  
Novel Drugs ◽  
Screening Protocol ◽  
Cost Efficient ◽  
Novel Drug

Although almost fully automated, the discovery of novel, effective, and safe drugs is still a long-term and highly expensive process. Consequently, the need for fleet, rational, and cost-efficient development of novel drugs is crucial, and nowadays the advanced in silico drug design methodologies seem to effectively meet these issues. The aim of this chapter is to provide a comprehensive overview of some of the current trends and advances in the in silico design of novel drug candidates with a special emphasis on 6-fluoroquinolone (6-FQ) antibacterials as potential novel Mycobacterium tuberculosis DNA gyrase inhibitors. In particular, the chapter covers some of the recent aspects of a wide range of in silico drug discovery approaches including multidimensional machine-learning methods, ligand-based and structure-based methodologies, as well as their proficient combination and integration into an intelligent virtual screening protocol for design and optimization of novel 6-FQ analogs.

scholarly journals Prediction of No Tropic Properties of Novel Drug Modafiendz using in-Silico Method

2020 ◽  
Vol 8 (2S12) ◽  
pp. 1-8
Keyword(s):  
In Silico ◽  
New Drugs ◽  
Drug Candidate ◽  
Healthy Individuals ◽  
Structure And Property ◽  
Drug Candidates ◽  
Nootropic Drug ◽  
Natural Drugs ◽  
Novel Drug ◽  
Gi Absorption

The development and approval of new drug is a tedious, expensive and highly time-consuming task. The demand of new drugs is increasing, and the development of natural drugs and traditional drugs are re-emerging as a new strategic task. The in-silico techniques have boosted the development of potential drug candidates. One important category of drugs is nootropes. It improves the cognitive function, memory, motivation and creativity in healthy individuals. The demand of the nootropic drugs has skyrocketed in past few decades. Modafiendz is a novel drug that is often used by the consumers as it is having similarity in structure and property with modafinil (Nootropic drug). But no major studies have been carried out on this molecule, so remains an investigatory molecule. There are several in-silico techniques that can be used to predict the likeness, metabolic activity and pharmacological property of a molecule. In the current study, realizing the importance of modafiendz, various properties of modafiendz have been predicted like metabolism site, ADME properties, metabolite prediction and DNA adduct formation tendencies.The properties of modafiendz were found to be similar to modafinil in various regards of drug likeability, bioavailability, blood brain permeability (BBB), GI absorption and site of metabolism (SOM). The study suggests modafiendz as a better nootropic drug candidate, when compared to modafinil.

scholarly journals In-Silico Interaction of Hydroxychloroquine Drug with Various Proteins of Coronavirus (SARS-CoV-2): A Computational Approaches to Combat COVID-19

2020 ◽  
Author(s):  
Rishee Kalaria ◽  
Hiren K. Patel
Keyword(s):  
Drug Interactions ◽  
Binding Affinity ◽  
Clinical Evaluation ◽  
In Silico ◽  
Docking Study ◽  
Spike Glycoprotein ◽  
Computational Approaches ◽  
Drug Candidates ◽  
Novel Drug

<p><i>In silico</i> docking study showed that hydroxychloroquine drug interactions with SARS-CoV2 show a higher binding affinity with spike glycoprotein and PLPRO protein compared to protein envelopes that could be ladder for potential targeting and synthesizing of another aniviral drug. <i>In silico</i> methods used in this study, the efficacy of a wide variety of repositioned and/or novel drug candidates could also be tested prior to clinical evaluation.</p>

scholarly journals In-Silico Interaction of Hydroxychloroquine Drug with Various Proteins of Coronavirus (SARS-CoV-2): A Computational Approaches to Combat COVID-19

2020 ◽  
Author(s):  
Rishee Kalaria ◽  
Hiren K. Patel
Keyword(s):  
Drug Interactions ◽  
Binding Affinity ◽  
Clinical Evaluation ◽  
In Silico ◽  
Docking Study ◽  
Spike Glycoprotein ◽  
Computational Approaches ◽  
Drug Candidates ◽  
Novel Drug

<p><i>In silico</i> docking study showed that hydroxychloroquine drug interactions with SARS-CoV2 show a higher binding affinity with spike glycoprotein and PLPRO protein compared to protein envelopes that could be ladder for potential targeting and synthesizing of another aniviral drug. <i>In silico</i> methods used in this study, the efficacy of a wide variety of repositioned and/or novel drug candidates could also be tested prior to clinical evaluation.</p>

scholarly journals Recent Developments in New Therapeutic Agents against Alzheimer and Parkinson Diseases: In-Silico Approaches

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2193
Author(s):  
Pedro Cruz-Vicente ◽  
Luís A. Passarinha ◽  
Samuel Silvestre ◽  
Eugenia Gallardo
Keyword(s):  
Clinical Trials ◽  
In Silico ◽  
Symptomatic Relief ◽  
Therapeutic Agents ◽  
Future Perspectives ◽  
Drug Candidates ◽  
Recent Developments ◽  
Progressive Neurodegeneration ◽  
Novel Drug ◽  
Parkinson Diseases

Neurodegenerative diseases (ND), including Alzheimer’s (AD) and Parkinson’s Disease (PD), are becoming increasingly more common and are recognized as a social problem in modern societies. These disorders are characterized by a progressive neurodegeneration and are considered one of the main causes of disability and mortality worldwide. Currently, there is no existing cure for AD nor PD and the clinically used drugs aim only at symptomatic relief, and are not capable of stopping neurodegeneration. Over the last years, several drug candidates reached clinical trials phases, but they were suspended, mainly because of the unsatisfactory pharmacological benefits. Recently, the number of compounds developed using in silico approaches has been increasing at a promising rate, mainly evaluating the affinity for several macromolecular targets and applying filters to exclude compounds with potentially unfavorable pharmacokinetics. Thus, in this review, an overview of the current therapeutics in use for these two ND, the main targets in drug development, and the primary studies published in the last five years that used in silico approaches to design novel drug candidates for AD and PD treatment will be presented. In addition, future perspectives for the treatment of these ND will also be briefly discussed.

Integrated in Silico Methods for the Design and Optimization of Novel Drug Candidates

2015 ◽  
pp. 269-317
Author(s):  
Nikola Minovski ◽  
Marjana Novič
Keyword(s):  
In Silico ◽  
Comprehensive Overview ◽  
Design And Optimization ◽  
Drug Candidates ◽  
In Silico Drug Design ◽  
Current Trends ◽  
Novel Drugs ◽  
Screening Protocol ◽  
Cost Efficient ◽  
Novel Drug

Although almost fully automated, the discovery of novel, effective, and safe drugs is still a long-term and highly expensive process. Consequently, the need for fleet, rational, and cost-efficient development of novel drugs is crucial, and nowadays the advanced in silico drug design methodologies seem to effectively meet these issues. The aim of this chapter is to provide a comprehensive overview of some of the current trends and advances in the in silico design of novel drug candidates with a special emphasis on 6-fluoroquinolone (6-FQ) antibacterials as potential novel Mycobacterium tuberculosis DNA gyrase inhibitors. In particular, the chapter covers some of the recent aspects of a wide range of in silico drug discovery approaches including multidimensional machine-learning methods, ligand-based and structure-based methodologies, as well as their proficient combination and integration into an intelligent virtual screening protocol for design and optimization of novel 6-FQ analogs.

Lead Molecule Prediction and Characterization for Designing MERS-CoV 3C-like Protease Inhibitors: An In silico Approach

2018 ◽  
Vol 15 (1) ◽  
pp. 82-88 ◽  
Author(s):  
Md. Mostafijur Rahman ◽  
Md. Bayejid Hosen ◽  
M. Zakir Hossain Howlader ◽  
Yearul Kabir
Keyword(s):  
Binding Energy ◽  
Middle East ◽  
Virtual Screening ◽  
In Silico ◽  
Screening Method ◽  
Middle East Respiratory Syndrome ◽  
Cytochrome P450 Enzymes ◽  
Drug Molecules ◽  
Essential Enzyme ◽  
Reduced Toxicity

Background: 3C-like protease also called the main protease is an essential enzyme for the completion of the life cycle of Middle East Respiratory Syndrome Coronavirus. In our study we predicted compounds which are capable of inhibiting 3C-like protease, and thus inhibit the lifecycle of Middle East Respiratory Syndrome Coronavirus using in silico methods. </P><P> Methods: Lead like compounds and drug molecules which are capable of inhibiting 3C-like protease was identified by structure-based virtual screening and ligand-based virtual screening method. Further, the compounds were validated through absorption, distribution, metabolism and excretion filtering. Results: Based on binding energy, ADME properties, and toxicology analysis, we finally selected 3 compounds from structure-based virtual screening (ZINC ID: 75121653, 41131653, and 67266079) having binding energy -7.12, -7.1 and -7.08 Kcal/mol, respectively and 5 compounds from ligandbased virtual screening (ZINC ID: 05576502, 47654332, 04829153, 86434515 and 25626324) having binding energy -49.8, -54.9, -65.6, -61.1 and -66.7 Kcal/mol respectively. All these compounds have good ADME profile and reduced toxicity. Among eight compounds, one is soluble in water and remaining 7 compounds are highly soluble in water. All compounds have bioavailability 0.55 on the scale of 0 to 1. Among the 5 compounds from structure-based virtual screening, 2 compounds showed leadlikeness. All the compounds showed no inhibition of cytochrome P450 enzymes, no blood-brain barrier permeability and no toxic structure in medicinal chemistry profile. All the compounds are not a substrate of P-glycoprotein. Our predicted compounds may be capable of inhibiting 3C-like protease but need some further validation in wet lab.

scholarly journals Phytochemicals as potential drug candidates for targeting SARS CoV 2 proteins, an in silico study

VirusDisease ◽  
2021 ◽  
Author(s):  
Anish Nag ◽  
Ritesh Banerjee ◽  
Rajshree Roy Chowdhury ◽  
Chandana Krishnapura Venkatesh
Keyword(s):  
In Silico ◽  
Potential Drug ◽  
Drug Candidates ◽  
In Silico Study

scholarly journals Application of Cryo-Electron Microscopy on Drug Discovery

2021 ◽  
Vol 27 (S1) ◽  
pp. 3250-3250
Author(s):  
Viswanath Vittaladevaram ◽  
Kranthi Kuruti
Keyword(s):  
Electron Microscopy ◽  
Protein Complexes ◽  
Lead Discovery ◽  
Biologically Relevant ◽  
Biological Targets ◽  
3 Dimensional ◽  
Drug Molecules ◽  
Cryo Electron Microscopy ◽  
Therapeutic Molecules ◽  
Novel Drug

AbstractThe key aspect for development of novel drug molecules is to perform structural determination of target molecule associated with its ligand. One such tool that provides insights towards structure of molecule is Cryo-electron microscopy which covers biological targets that are intractable. Examination of proteins can be carried out in native state, as the samples are frozen at -175 degree Celsius i.e. cryogenic temperatures. In addition to this, there were no limits for molecular and functional structures of proteins that can be imagined in 3-dimensional form. This includes ligands which unravel mechanisms that are biologically relevant. This will enable to better understand the mechanisms that are used for development of new therapeutics. Application of Cryo-electron microscopy is not limited to protein complexes and is considered as non-specific. Intervention of Cryo-EM would allow to analyse the structures and also able to dissect the interaction with therapeutic molecules. The study determines the usage of cryo-EM for providing resolutions that are acceptable for lead discovery. It also provides support for lead optimization and also for discovery of vaccines and therapeutics.

scholarly journals Integrated network analysis identifying potential novel drug candidates and targets for Parkinson's disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pusheng Quan ◽  
Kai Wang ◽  
Shi Yan ◽  
Shirong Wen ◽  
Chengqun Wei ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Target ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Control Group ◽  
Drug Candidates ◽  
Novel Drug

AbstractThis study aimed to identify potential novel drug candidates and targets for Parkinson’s disease. First, 970 genes that have been reported to be related to PD were collected from five databases, and functional enrichment analysis of these genes was conducted to investigate their potential mechanisms. Then, we collected drugs and related targets from DrugBank, narrowed the list by proximity scores and Inverted Gene Set Enrichment analysis of drug targets, and identified potential drug candidates for PD treatment. Finally, we compared the expression distribution of the candidate drug-target genes between the PD group and the control group in the public dataset with the largest sample size (GSE99039) in Gene Expression Omnibus. Ten drugs with an FDR < 0.1 and their corresponding targets were identified. Some target genes of the ten drugs significantly overlapped with PD-related genes or already known therapeutic targets for PD. Nine differentially expressed drug-target genes with p < 0.05 were screened. This work will facilitate further research into the possible efficacy of new drugs for PD and will provide valuable clues for drug design.

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