scholarly journals Extensive Reliability Evaluation of Docking-Based Target-Fishing Strategies

2019 ◽  
Vol 20 (5) ◽  
pp. 1023 ◽  
Author(s):  
Margherita Lapillo ◽  
Tiziano Tuccinardi ◽  
Adriano Martinelli ◽  
Marco Macchia ◽  
Antonio Giordano ◽  
...  
Keyword(s):  
Small Molecule ◽  
Protein Structures ◽  
Drug Repurposing ◽  
Protein Targets ◽  
Drug Candidates ◽  
Fishing Strategies ◽  
Benchmark Database ◽  
Speed Up ◽  
Actual Target ◽  
Target Fishing

The development of target-fishing approaches, aimed at identifying the possible protein targets of a small molecule, represents a hot topic in medicinal chemistry. A successful target-fishing approach would allow for the elucidation of the mechanism of action of all therapeutically interesting compounds for which the actual target is still unknown. Moreover, target-fishing would be essential for preventing adverse effects of drug candidates, by predicting their potential off-targets, and it would speed up drug repurposing campaigns. However, due to the huge number of possible protein targets that a small-molecule might interact with, experimental target-fishing approaches are out of reach. In silico target-fishing represents a valuable alternative, and examples of receptor-based approaches, exploiting the large number of crystallographic protein structures determined to date, have been reported in the literature. To the best of our knowledge, no proper evaluation of such approaches is, however, reported yet. In the present work, we extensively assessed the reliability of docking-based target-fishing strategies. For this purpose, a set of X-ray structures belonging to different targets was selected, and a dataset of compounds, including 10 experimentally active ligands for each target, was created. A target-fishing benchmark database was then obtained, and used to assess the performance of 13 different docking procedures, in identifying the correct target of the dataset ligands. Moreover, a consensus docking-based target-fishing strategy was developed and evaluated. The analysis highlighted that specific features of the target proteins could affect the reliability of the protocol, which however, proved to represent a valuable tool in the proper applicability domain. Our study represents the first extensive performance assessment of docking-based target-fishing approaches, paving the way for the development of novel efficient receptor-based target fishing strategies.

scholarly journals Recent Advances in In Silico Target Fishing

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5124 ◽  
Author(s):  
Salvatore Galati ◽  
Miriana Di Stefano ◽  
Elisa Martinelli ◽  
Giulio Poli ◽  
Tiziano Tuccinardi
Keyword(s):  
Drug Discovery ◽  
In Silico ◽  
Drug Targets ◽  
Biological Activities ◽  
Protein Structures ◽  
Drug Repurposing ◽  
Specific Protein ◽  
Protein Targets ◽  
Drug Candidates ◽  
Target Fishing

In silico target fishing, whose aim is to identify possible protein targets for a query molecule, is an emerging approach used in drug discovery due its wide variety of applications. This strategy allows the clarification of mechanism of action and biological activities of compounds whose target is still unknown. Moreover, target fishing can be employed for the identification of off targets of drug candidates, thus recognizing and preventing their possible adverse effects. For these reasons, target fishing has increasingly become a key approach for polypharmacology, drug repurposing, and the identification of new drug targets. While experimental target fishing can be lengthy and difficult to implement, due to the plethora of interactions that may occur for a single small-molecule with different protein targets, an in silico approach can be quicker, less expensive, more efficient for specific protein structures, and thus easier to employ. Moreover, the possibility to use it in combination with docking and virtual screening studies, as well as the increasing number of web-based tools that have been recently developed, make target fishing a more appealing method for drug discovery. It is especially worth underlining the increasing implementation of machine learning in this field, both as a main target fishing approach and as a further development of already applied strategies. This review reports on the main in silico target fishing strategies, belonging to both ligand-based and receptor-based approaches, developed and applied in the last years, with a particular attention to the different web tools freely accessible by the scientific community for performing target fishing studies.

scholarly journals Virtual Screening of Some Antivirals That Can Be Repurposed As Potential Effective Drugs against SARS-CoV-2

2020 ◽  
Author(s):  
Mohammad Rejaur Rahman ◽  
Anik Banik ◽  
Ishtiak Malique Chowdhury ◽  
Emran Sajib ◽  
Sanchita Sarkar
Keyword(s):  
Rna Binding ◽  
Viral Infections ◽  
Toxicity Testing ◽  
Drug Repurposing ◽  
Drug Candidates ◽  
Docking Method ◽  
Speed Up ◽  
Coronavirus Infection ◽  
Effective Drugs ◽  
Drug Similarity

<p>SARS-CoV-2 has triggered a big epidemic among people around the world and it is the newest in the sequence to be prevalent among other infectious diseases. Drug repurposing concept has been utilized effectively for numerous viral infections. Considering the situation and the urgency, the idea of drug repurposing for coronavirus infection (COVID-19) is also being studied. Screening with molecular docking method for 29 antiviral drugs was performed against SARSCoV-2 primary protease proteins (MPP), spike ecto-domain, spike receptor binding domain, Nsp9 RNA binding protein,and HR2 domain. Among these drugs, Indinavir, Sorivudine, Cidofovir and Darunavir show minimum docking scores with all key proteins in terms of least binding energy. For ADME (Absorption, Distribution, Metabolism, and Excretion) analysis, the top 4 drug candidates were further used to examine their drug profiles for suitability against SARS-CoV-2. The toxicity testing of top drug candidates showed no significant carcinogenic, mutagenic or skin irritating impacts. Indinavir may possess some complexity to heart. In addition, the drug similarity prediction revealed several approved structural analogues such as Telbivudine, Tenofovir, Amprenavir, Fosamprenavir etc which also could be used to treat viral infections. The study may speed up the findings of therapeutics against SARS-CoV-2. <br></p>

scholarly journals Virtual Screening of Some Antivirals That Can Be Repurposed As Potential Effective Drugs against SARS-CoV-2

2020 ◽  
Author(s):  
Mohammad Rejaur Rahman ◽  
Anik Banik ◽  
Ishtiak Malique Chowdhury ◽  
Emran Sajib ◽  
Sanchita Sarkar
Keyword(s):  
Rna Binding ◽  
Viral Infections ◽  
Toxicity Testing ◽  
Drug Repurposing ◽  
Drug Candidates ◽  
Docking Method ◽  
Speed Up ◽  
Coronavirus Infection ◽  
Effective Drugs ◽  
Drug Similarity

<p>SARS-CoV-2 has triggered a big epidemic among people around the world and it is the newest in the sequence to be prevalent among other infectious diseases. Drug repurposing concept has been utilized effectively for numerous viral infections. Considering the situation and the urgency, the idea of drug repurposing for coronavirus infection (COVID-19) is also being studied. Screening with molecular docking method for 29 antiviral drugs was performed against SARSCoV-2 primary protease proteins (MPP), spike ecto-domain, spike receptor binding domain, Nsp9 RNA binding protein,and HR2 domain. Among these drugs, Indinavir, Sorivudine, Cidofovir and Darunavir show minimum docking scores with all key proteins in terms of least binding energy. For ADME (Absorption, Distribution, Metabolism, and Excretion) analysis, the top 4 drug candidates were further used to examine their drug profiles for suitability against SARS-CoV-2. The toxicity testing of top drug candidates showed no significant carcinogenic, mutagenic or skin irritating impacts. Indinavir may possess some complexity to heart. In addition, the drug similarity prediction revealed several approved structural analogues such as Telbivudine, Tenofovir, Amprenavir, Fosamprenavir etc which also could be used to treat viral infections. The study may speed up the findings of therapeutics against SARS-CoV-2. <br></p>

scholarly journals ASSESSING THE ROLE OF ARTIFICIAL INTELLIGENCE IN THE DESIGN OF DRUG DELIVERY SYSTEMS

2020 ◽  
Vol 4 (12) ◽  
Author(s):  
Abdul Waheed ◽  
Ashwin K ◽  
Hima Bindu M
Keyword(s):  
Artificial Intelligence ◽  
Drug Delivery ◽  
Data Interpretation ◽  
Transport Systems ◽  
Diagnostic Strategies ◽  
Drug Candidates ◽  
Speed Up ◽  
Small Molecule Modulator ◽  
Target Fishing

Over ten years, increasing the interest has been fascinated towards the appeal of intelligent retrieval (IR) technology for data interpretation and illuminate the biological or transmitted information, speed up drug invention, and pinpointing of the selective small-molecule modulator control or rare particle and projection of their behavior. To make use of biomaterials, synthetic resin, fats, along IR is upcoming for the manufacture of drug deliverables. The request of the computerized workflows and databases for quick calculation of the vast amounts of data and artificial neural networks (ANNs) for growth of the narrative proposition and treatment schemes, forecast of disease development, and judgment of the pharmacological description of drug candidates may consequently improve treatment outcomes. Target fishing (TG) by quick projection or identification of the biological quarry might be of great help for linking quarry to the new substance.AI and TF methods in union with human knowledge may indeed transform the present-day diagnostic strategies, meanwhile verifying approaches are necessary to overcome the possible challenges and make certain higher perfection. In this review, the importance of AI and TF in the growth of drugs and transport systems and the possible challenging topics have been spotlighted. Keywords: Artificial intelligence; biomaterials, polymers, lipids, Drug Delivery.

scholarly journals Drug Repurposing of Approved Drugs Elbasvir, Ledipasvir, Paritaprevir, Velpatasvir, Antrafenine and Ergotamine for Combating COVID19

2020 ◽  
Author(s):  
Vishal Mevada ◽  
Pravin Dudhagara ◽  
Himani Gandhi ◽  
Nilam Vaghamshi ◽  
Urvisha Beladiya ◽  
...  
Keyword(s):  
Protein Structures ◽  
Drug Repurposing ◽  
Drug Candidates ◽  
Sequential Screening ◽  
Drug Molecules ◽  
Single Target ◽  
Approved Drugs ◽  
Hiv Drugs ◽  
Anti Hiv ◽  
Country Office

<p>Pneumonia of unknown cause detected in Wuhan, China was first reported to the WHO Country Office in China on 31 December 2019. The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020. Currently, there is no Vaccine against COVID-19 pandemic and infection is spreading worldwide vary rapidly there is an exigent requirement of practicable drug treatment. Drug repurposing is one of the most promising approaches for that. Many reports are available with <i>in silico</i> drug repurposing but the majority of them engrossed on a single target. The present study aimed at screening the approved against Covid19 protein and extract the combination of operational comprehensively. A total of 1735 drug molecules against all COVID19 protein structures and sequential screening recognize the better potential of anti-HCV drugs over anti-HIV drugs. The study designated Elbasvir, Ledipasvir, Paritaprevir, Velpatasvir, Antrafenine Ergotamin as promising drug candidates for covid19 treatment. The computational analysis also reveled the better potential of proposed drugs over the currently used drug combination for COVID19 drugs. </p>

scholarly journals Repurposing the Ebola and Marburg Virus Inhibitors Tilorone, Quinacrine and Pyronaridine: In vitro Activity Against SARS-CoV-2 and Potential Mechanisms

2020 ◽  
Author(s):  
Ana C. Puhl ◽  
Ethan James Fritch ◽  
Thomas R. Lane ◽  
Longping V. Tse ◽  
Boyd L. Yount ◽  
...  
Keyword(s):  
Cell Lines ◽  
Small Molecule ◽  
Ebola Virus ◽  
Early Stage ◽  
Drug Repurposing ◽  
Marburg Virus ◽  
Small Molecule Drugs ◽  
Speed Up

AbstractSARS-CoV-2 is a newly identified virus that has resulted in over 1.3 M deaths globally and over 59 M cases globally to date. Small molecule inhibitors that reverse disease severity have proven difficult to discover. One of the key approaches that has been widely applied in an effort to speed up the translation of drugs is drug repurposing. A few drugs have shown in vitro activity against Ebola virus and demonstrated activity against SARS-CoV-2 in vivo. Most notably the RNA polymerase targeting remdesivir demonstrated activity in vitro and efficacy in the early stage of the disease in humans. Testing other small molecule drugs that are active against Ebola virus would seem a reasonable strategy to evaluate their potential for SARS-CoV-2. We have previously repurposed pyronaridine, tilorone and quinacrine (from malaria, influenza, and antiprotozoal uses, respectively) as inhibitors of Ebola and Marburg virus in vitro in HeLa cells and of mouse adapted Ebola virus in mouse in vivo. We have now tested these three drugs in various cell lines (VeroE6, Vero76, Caco-2, Calu-3, A549-ACE2, HUH-7 and monocytes) infected with SARS-CoV-2 as well as other viruses (including MHV and HCoV 229E). The compilation of these results indicated considerable variability in antiviral activity observed across cell lines. We found that tilorone and pyronaridine inhibited the virus replication in A549-ACE2 cells with IC50 values of 180 nM and IC50 198 nM, respectively. We have also tested them in a pseudovirus assay and used microscale thermophoresis to test the binding of these molecules to the spike protein. They bind to spike RBD protein with Kd values of 339 nM and 647 nM, respectively. Human Cmax for pyronaridine and quinacrine is greater than the IC50 hence justifying in vivo evaluation. We also provide novel insights into their mechanism which is likely lysosomotropic.

Application of Artificial Intelligence in Drug Repurposing: A mini-review

2021 ◽  
Vol 01 ◽  
Author(s):  
Gurudeeban Selvaraj ◽  
Satyavani Kaliamurthi ◽  
Gilles H. Peslherbe ◽  
Dong-Qing Wei
Keyword(s):  
Artificial Intelligence ◽  
Drug Repositioning ◽  
Target Identification ◽  
Drug Repurposing ◽  
Search Term ◽  
Biomedical Data ◽  
Drug Candidates ◽  
Drug Target Identification ◽  
Speed Up ◽  
Tools And Techniques

Background and aim: Advancement of extra-ordinary biomedical data (genomics, proteomics, metabolomics, drug libraries, and patient care data), evolution of super-computers, and continuous development of new algorithms that lead to a generous revolution in artificial intelligence (AI). Currently, many biotech and pharmaceutical companies made reasonable investments in and have co-operation with AI companies and increasing the chance of better healthcare tools development, includes biomarker and drug target identification, designing a new class of drugs and drug repurposing. Thus, the study is intended to project the pros and cons of AI in the application of drug repositioning. Methods: Using the search term “AI” and “drug repurposing” the relevant literatures retrieved and reviewed from different sources includes PubMed, Google Scholar, and Scopus. Results: Drug discovery is a lengthy process, however, leveraging the AI approaches in drug repurposing via quick virtual screening may enhance and speed-up the identification of potential drug candidates against communicable and non-communicable diseases. Therefore, in this mini-review, we have discussed different algorithms, tools and techniques, advantages, limitations on predicting the target in repurposing a drug. Conclusions: AI technology in drug repurposing with the association of pharmacology can efficiently identify drug candidates against pandemic diseases.

scholarly journals Drug Repurposing of Approved Drugs Elbasvir, Ledipasvir, Paritaprevir, Velpatasvir, Antrafenine and Ergotamine for Combating COVID19

2020 ◽  
Author(s):  
Vishal Mevada ◽  
Pravin Dudhagara ◽  
Himani Gandhi ◽  
Nilam Vaghamshi ◽  
Urvisha Beladiya ◽  
...  
Keyword(s):  
Protein Structures ◽  
Drug Repurposing ◽  
Drug Candidates ◽  
Sequential Screening ◽  
Drug Molecules ◽  
Single Target ◽  
Approved Drugs ◽  
Hiv Drugs ◽  
Anti Hiv ◽  
Country Office

<p>Pneumonia of unknown cause detected in Wuhan, China was first reported to the WHO Country Office in China on 31 December 2019. The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020. Currently, there is no Vaccine against COVID-19 pandemic and infection is spreading worldwide vary rapidly there is an exigent requirement of practicable drug treatment. Drug repurposing is one of the most promising approaches for that. Many reports are available with <i>in silico</i> drug repurposing but the majority of them engrossed on a single target. The present study aimed at screening the approved against Covid19 protein and extract the combination of operational comprehensively. A total of 1735 drug molecules against all COVID19 protein structures and sequential screening recognize the better potential of anti-HCV drugs over anti-HIV drugs. The study designated Elbasvir, Ledipasvir, Paritaprevir, Velpatasvir, Antrafenine Ergotamin as promising drug candidates for covid19 treatment. The computational analysis also reveled the better potential of proposed drugs over the currently used drug combination for COVID19 drugs. </p>

scholarly journals Ro5 Bioactivity Lab: Identification of Drug Candidates for COVID-19

2020 ◽  
Author(s):  
Zeyu Yang ◽  
Orestis Bastas ◽  
Mikhail Demtchenko ◽  
Aurimas Pabrinkis ◽  
Cooper Stergis Jamieson ◽  
...  
Keyword(s):  
Small Molecules ◽  
Antiviral Treatment ◽  
Drug Repurposing ◽  
Protein Targets ◽  
Docking Simulations ◽  
The Public ◽  
Drug Candidates ◽  
Potential Inhibitors ◽  
3Cl Protease ◽  
Vast Range

The public health emergency known as the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a large number of deaths worldwide and major socioeconomic disruption. To date, no broadly effective antiviral treatment or vaccine has been developed for COVID-19. In response to this dire situation, Ro5 deployed its AI Lab to accelerate the search for potential treatments. This report focuses on our use of the Ro5 Bioactivity model, which has been designed to predict the inhibitory activity of small molecules against protein targets. The model screened a vast range of compounds <i>in silico</i> to uncover potential inhibitors of the SARS-CoV-2 3CL protease. We hereby present the most propitious candidates from this screen. The highest-ranking molecules include Nelfinavir, Saquinavir, Itacitinib, Kynostatin-272, BOG-INS-6c2-1, and BEN-VAN-d2b-11. Subsequent docking simulations corroborate their plausibility as 3CLpro inhibitors. Nelfinavir and Itacitinib hold the most promise for drug repurposing, among all the molecules proposed herein, due to their high predicted inhibition and affinity against the 3CL protease, favourable pharmacokinetics, and encouraging experimental data for treating viral replication and hyperinflammation, respectively.

scholarly journals Drug Repurposing of Approved Drugs Elbasvir, Ledipasvir, Paritaprevir, Velpatasvir, Antrafenine and Ergotamine for Combating COVID19

2020 ◽  
Author(s):  
Vishal Mevada ◽  
Pravin Dudhagara ◽  
Himani Gandhi ◽  
Nilam Vaghamshi ◽  
Urvisha Beladiya ◽  
...  
Keyword(s):  
Protein Structures ◽  
Drug Repurposing ◽  
Drug Candidates ◽  
Sequential Screening ◽  
Drug Molecules ◽  
Single Target ◽  
Approved Drugs ◽  
Hiv Drugs ◽  
Anti Hiv ◽  
Country Office

<p>Pneumonia of unknown cause detected in Wuhan, China was first reported to the WHO Country Office in China on 31 December 2019. The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020. Currently, there is no Vaccine against COVID-19 pandemic and infection is spreading worldwide vary rapidly there is an exigent requirement of practicable drug treatment. Drug repurposing is one of the most promising approaches for that. Many reports are available with <i>in silico</i> drug repurposing but the majority of them engrossed on a single target. The present study aimed at screening the approved against Covid19 protein and extract the combination of operational comprehensively. A total of 1735 drug molecules against all COVID19 protein structures and sequential screening recognize the better potential of anti-HCV drugs over anti-HIV drugs. The study designated Elbasvir, Ledipasvir, Paritaprevir, Velpatasvir, Antrafenine Ergotamin as promising drug candidates for covid19 treatment. The computational analysis also reveled the better potential of proposed drugs over the currently used drug combination for COVID19 drugs. </p>

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