In silico drug repurposing of FDA-approved drugs to predict new inhibitors for drug resistant T315I mutant and wild-type BCR-ABL1: A virtual screening and molecular dynamics study

2017 ◽  
Vol 74 ◽  
pp. 234-240 ◽  
Author(s):  
Farzin Sohraby ◽  
Milad Bagheri ◽  
Masoud Aliyar ◽  
Hassan Aryapour
Keyword(s):  
Molecular Dynamics ◽  
Virtual Screening ◽  
In Silico ◽  
Drug Repurposing ◽  
Drug Resistant ◽  
Wild Type ◽  
Approved Drugs ◽  
Fda Approved Drugs

Repurposing FDA-approved Drugs Targeting SARS-CoV2 3CLpro: a study by applying Virtual Screening, Molecular Dynamics, MM-PBSA Calculations and Covalent Docking

2022 ◽  
Vol 19 ◽  
Author(s):  
Igor José dos Santos Nascimento ◽  
Thiago Mendonça de Aquino ◽  
Edeildo Ferreira da Silva-Júnior
Keyword(s):  
Molecular Dynamics ◽  
Virtual Screening ◽  
In Silico ◽  
Structural Integrity ◽  
Inhibition Mechanism ◽  
Zinc Database ◽  
Covalent Docking ◽  
Approved Drugs ◽  
Fda Approved Drugs

Background: Since the end of 2019, the etiologic agent SAR-CoV-2 responsible for one of the most significant epidemics in history has caused severe global economic, social, and health damages. The drug repurposing approach and application of Structure-based Drug Discovery (SBDD) using in silico techniques are increasingly frequent, leading to the identification of several molecules that may represent promising potential. Method: In this context, here we use in silico methods of virtual screening (VS), pharmacophore modeling (PM), and fragment-based drug design (FBDD), in addition to molecular dynamics (MD), molecular mechanics/Poisson-Boltzmann surface area (MM -PBSA) calculations, and covalent docking (CD) for the identification of potential treatments against SARS-CoV-2. We initially validated the docking protocol followed by VS in 1,613 FDA-approved drugs obtained from the ZINC database. Thus, we identified 15 top hits, of which three of them were selected for further simulations. In parallel, for the compounds with a fit score value ≤ of 30, we performed the FBDD protocol, where we designed 12 compounds Result: By applying a PM protocol in the ZINC database, we identified three promising drug candidates. Then, the 9 top hits were evaluated in simulations of MD, MM-PBSA, and CD. Subsequently, MD showed that all identified hits showed stability at the active site without significant changes in the protein's structural integrity, as evidenced by the RMSD, RMSF, Rg, SASA graphics. They also showed interactions with the catalytic dyad (His41 and Cys145) and other essential residues for activity (Glu166 and Gln189) and high affinity for MM-PBSA, with possible covalent inhibition mechanism. Conclution: Finally, our protocol helped identify potential compounds wherein ZINC896717 (Zafirlukast), ZINC1546066 (Erlotinib), and ZINC1554274 (Rilpivirine) were more promising and could be explored in vitro, in vivo, and clinical trials to prove their potential as antiviral agents.

In Silico Modeling of FDA-Approved Drugs for Discovery of Therapies Against Neglected Diseases: A Drug Repurposing Approach

2019 ◽  
pp. 625-648 ◽  
Author(s):  
Carolina L. Belllera ◽  
María L. Sbaraglini ◽  
Lucas N. Alberca ◽  
Juan I. Alice ◽  
Alan Talevi
Keyword(s):  
In Silico ◽  
Drug Repurposing ◽  
Neglected Diseases ◽  
In Silico Modeling ◽  
Approved Drugs ◽  
Fda Approved Drugs

scholarly journals Drug Repurposing Commonly Against Dengue Virus Capsid and SARS-CoV-2 Nucleocapsid: An in Silico Approach

2020 ◽  
Author(s):  
Debica Mukherjee ◽  
Rupesh Roy ◽  
UPASANA RAY
Keyword(s):  
Dengue Virus ◽  
Capsid Protein ◽  
In Silico ◽  
Rna Binding ◽  
Drug Repurposing ◽  
Virus Capsid ◽  
Approved Drugs ◽  
Full Swing ◽  
Fda Approved Drugs ◽  
Virus Capsid Protein

<p></p><p>In the middle of SARS-CoV-2 pandemic, dengue virus (DENV) is giving a silent warning as the season approaches nearer. There is no specific antiviral against DENV for use in the clinics. Thus, considering these facts we can potentially face both these viruses together increasing the clinical burden. The search for anti-viral drugs against SARS-CoV-2 is in full swing and repurposing of already ‘in-use’ drugs against other diseases or COVID-19 has drawn significant attention. Earlier we had reported few FDA approved anti-viral and anti-microbial drugs that could be tested for binding with SARS-CoV-2 nucleocapsid N terminal domain. We explored the possibility of interactions of the drugs screened for SARS-CoV2 with Dengue virus capsid protein. We report five FDA approved drugs that were seen to be docking onto the SARS-CoV-2 nucleocapsid RNA binding domain, also docking well with DENV capsid protein on the RNA binding site and/or the capsid’s membrane fusion domain. Thus, the present study proposes these five drugs as common antiviral candidates against both SARS-CoV-2 and DENV although the <i>in silico</i> study is subject to further validations.</p><br><p></p>

scholarly journals Virtual Screening Enabled Selection of Antiviral Agents Against Covid-19 Disease Targeting Coronavirus Endoribonuclease NendoU: Plausible Mechanistic Interventions in the Treatment of New Virus Strain

2020 ◽  
Author(s):  
Gaurav Joshi ◽  
Ramarao Poduri
Keyword(s):  
Virtual Screening ◽  
Homo Sapiens ◽  
Antiviral Agents ◽  
Drug Repurposing ◽  
Experimental Drugs ◽  
Experimental Drug ◽  
Investigational Drugs ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Selection Of

<p>SARS-CoV-2 is the seventh coronavirus that is reported to cause infection in Homo sapiens. Considering its pandemic nature, development of newer and effective therapeutic strategies, drug repurposing in combination with target validation approaches has led to the identification of new antiviral molecules. In current work, we performed virtual screening and molecular docking of 8548 ligands on target protein coronavirus endoribonuclease NendoU (3VWW). The molecules selected includes FDA approved drugs along with investigational or experimental drugs recommended for anticancer, antiviral, antimicrobial, and antiprotozoal properties. The thorough selection and their rationality with Covid-19 led us to propose that FDA approved drug DB00876 (Eprosartan), Investigational drugs DB15063 (Inarigivir soproxil), DB12307 (Foretinib) and DB01813 an experimental drug may be repurposed for treatment of Covid-19 disease.</p>

scholarly journals Virtual Screening of FDA Approved Drugs Against Nsp15 Endoribonuclease from SARS CoV-2

2020 ◽  
Author(s):  
Althaf Shaik ◽  
Nalini Natarajan ◽  
Sivapriya Kirubakaran ◽  
Vijay Thiruvenkatam
Keyword(s):  
Crystal Structure ◽  
Molecular Dynamics ◽  
Virtual Screening ◽  
Computational Approach ◽  
Important Target ◽  
Structure Solution ◽  
Wet Lab ◽  
Approved Drugs ◽  
Dynamics Simulations ◽  
Fda Approved Drugs

<p>This manuscript shows a detailed computational approach of carefully curated drugs that can potentially act against Nsp15, an endoribonuclease necessary for SARS-CoV2 multiplication. In our work, we have considered maximum resources available on Nsp15 including the recent crystal structure solution of the protein. Owing to the increase in demand for a cure for COVID-19, we have attempted to virtually screen an important target of SARS-CoV2 using the pre-existing FDA approved drugs. The main advantage of our work is our multi-step approach in validating our hits. We have performed initial High Throughput Virtual Screening (HTVS) of 2910 drugs. The top 20 hits were subjected to rigorous molecular docking and molecular dynamics simulations yielding a final number of 5 potential hits. In this global emergency, we have made a humble yet critical attempt by undertaking this work; we hope that our work once published may be of help in carrying out appropriate wet-lab work. </p><p></p>We declare that this manuscript is original, has not been published before and is not currently being considered for publication elsewhere."

scholarly journals Virtual Screening of FDA Approved Drugs Against Nsp15 Endoribonuclease from SARS CoV-2

2020 ◽  
Author(s):  
Althaf Shaik ◽  
Nalini Natarajan ◽  
Sivapriya Kirubakaran ◽  
Vijay Thiruvenkatam
Keyword(s):  
Crystal Structure ◽  
Molecular Dynamics ◽  
Virtual Screening ◽  
Computational Approach ◽  
Important Target ◽  
Structure Solution ◽  
Wet Lab ◽  
Approved Drugs ◽  
Dynamics Simulations ◽  
Fda Approved Drugs

<p>This manuscript shows a detailed computational approach of carefully curated drugs that can potentially act against Nsp15, an endoribonuclease necessary for SARS-CoV2 multiplication. In our work, we have considered maximum resources available on Nsp15 including the recent crystal structure solution of the protein. Owing to the increase in demand for a cure for COVID-19, we have attempted to virtually screen an important target of SARS-CoV2 using the pre-existing FDA approved drugs. The main advantage of our work is our multi-step approach in validating our hits. We have performed initial High Throughput Virtual Screening (HTVS) of 2910 drugs. The top 20 hits were subjected to rigorous molecular docking and molecular dynamics simulations yielding a final number of 5 potential hits. In this global emergency, we have made a humble yet critical attempt by undertaking this work; we hope that our work once published may be of help in carrying out appropriate wet-lab work. </p><p></p>We declare that this manuscript is original, has not been published before and is not currently being considered for publication elsewhere."

scholarly journals Identification of new inhibitors of the toxoplasma gondii by using in-silico drug repurposing

2019 ◽  
Author(s):  
Mosleh Kadkhodamohammadi ◽  
Milad Jaberi ◽  
Reza Babaei akerdi ◽  
Masoud Aliyar
Keyword(s):  
Protein Kinase ◽  
Toxoplasma Gondii ◽  
In Silico ◽  
Drug Repurposing ◽  
Dependent Protein Kinase ◽  
Calcium Dependent ◽  
Dependent Protein ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Calcium Dependent Protein Kinase

AbstractIntroductionThe common treatment for toxoplasmosis was pyrimethamine. In recent years, it has been found that this parasite is getting resistant to this treatment, therefore urgent alternative treatments are needed.Material and MethodsIn this study, by using drug repurposing and in silico methods we tried to make a selective treatment by inhibiting the Calcium-Dependent Protein Kinase 1 from Toxoplasma gondii which doesn’t exist in mammalians. We screened the FDA approved drugs by molecular docking and after ranking them by their binding energies and inspecting the top scored ones, we chose Cefpiramide, Ceftriaxone and Cefotiam as the hit compounds. After that, we used molecular dynamics simulations to test the hit compounds in a much more realistic environment.ResultsBy analyzing the results, we found that all of the hit compounds and good and can bind strongly to the active site of the protein. Therefore, they can be potential candidates for inhibiting Calcium-Dependent Protein Kinase 1 from Toxoplasma gondii.ConclusionMoreover, because the predicted compounds are FDA approved drugs, their toxicity profiles are well known and their newly predicted use can be tested in clinical trials.

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