scholarly journals Potential efficacy of existing drug molecules against severe fever with thrombocytopenia syndrome virus: an in silico study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shilpa Chatterjee ◽  
Choon-Mee Kim ◽  
Dong-Min Kim
Keyword(s):  
Binding Energy ◽  
In Silico ◽  
Drug Repurposing ◽  
Biological Evaluation ◽  
Energy Calculation ◽  
L Protein ◽  
Drug Molecules ◽  
Potential Efficacy ◽  
In Silico Study ◽  
Severe Fever

AbstractSevere fever with thrombocytopenia syndrome (SFTS) is a zoonotic disease caused by the SFTS virus (SFTSV). SFTS can be considered a life-threatening notifiable infectious disease. The unavailability of specific therapeutics encourages the investigation of potential efficacy of existing drugs against this infection. Drug repurposing was done by performing  virtual screening of already established drug molecules followed by 100 ns molecular dynamics simulations and molecular mechanics Poisson–Boltzmann surface area–based binding-energy calculation by targeting the SFTS L protein. On the basis of binding energy and protein–ligand interactions, top 10 promising hits were identified, showing stable binding with SFTS L protein. Further 100 ns atomistic MD simulation refined the hits from top 10 to top 4 with docking-based binding energy lesser than −8.0 kcal/mol toward the SFTS L protein and engaged in π–π interactions with pivotal amino acid residues. Various parameters and binding affinity of top 4 ligands towards L protein was computed. Ligand zaltoprofen exhibited best binding energy −220.095 kJ/mol. The present work is the first in silico study to assess bromfenac, cinchophen, elliptinium, and zaltoprofen; four promising hits against SFTS. Nonetheless, further proper biological evaluation is necessary to determine their efficacy against SFTS.

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.

Imino‐2H‐chromene based derivatives as potential anti‐Alzheimer’s agents: Design, synthesis, biological evaluation and in silico study

2021 ◽  
Author(s):  
Mahshid Attarroshan ◽  
Omidreza Firuzi ◽  
Aida Iraji ◽  
Shahrzad Sharifi ◽  
Marjan Tavakkoli ◽  
...  
Keyword(s):  
In Silico ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
In Silico Study

Synthesis, biological evaluation and in silico study of bis-thiourea derivatives as anticancer, antimalarial and antimicrobial agents

2017 ◽  
Vol 26 (12) ◽  
pp. 3136-3148 ◽  
Author(s):  
Ratchanok Pingaew ◽  
Nujarin Sinthupoom ◽  
Prasit Mandi ◽  
Veda Prachayasittikul ◽  
Rungrot Cherdtrakulkiat ◽  
...  
Keyword(s):  
In Silico ◽  
Antimicrobial Agents ◽  
Biological Evaluation ◽  
Thiourea Derivatives ◽  
In Silico Study

scholarly journals IN SILICO STUDY OF ARYL EUGENOL DERIVATIVES AS ANTI-COLORECTAL CANCER BY INDUCING OF APOPTOSIS

2017 ◽  
Vol 10 (12) ◽  
pp. 345
Author(s):  
Fadilah Fadilah ◽  
Arry Yanuar ◽  
Ade Arsianti ◽  
Retnosari Andrajati ◽  
Erni Hernawati Purwaningsih
Keyword(s):  
Binding Energy ◽  
In Silico ◽  
Computer Software ◽  
Data Bank ◽  
The Body ◽  
Software Applications ◽  
In Silico Admet ◽  
In Silico Study ◽  
Abnormal Cells ◽  
Cancer Tissues

Objective: Apoptosis is one method the body uses to get rid of unneeded or abnormal cells, but cancer cells have strategies to avoid apoptosis. Apoptosis inducers can get around these strategies to cause the death of cancer cells.Methods: We screened some derivatives aryl eugenol based on their interactions with Bcl-2 in many cancer tissues, using computer software applications (in silico method) to determine the best compounds. The docking experiment on Bcl-2 (Protein Data Bank ID 4LXD) was carried out by suitably positioning the energy-minimized ligand in the active site while carefully monitoring non-bonded interactions of the ligand enzyme.Results: The resulting ligand-receptor complex was docked using the Autodock Vina software. Docking results based free binding energy, EUGACl (21), EUASABr (17), EUGEABr (19), and EUASACL (17), has the lowest binding energy than navitoclax and binds significantly to BCL 2. In silico ADMET predictions revealed that except SA, ASA, and GEA, all other compounds had minimal toxic effects and had good absorption as well as solubility characteristics.Conclusion: These compounds of aryl eugenol (17, 19, and 21) may serve as a potential lead compound for developing new anticancer as apoptosis inducers.

Preparation and biological evaluation of 99mTc N-histamine as a model for brain imaging: in silico study and preclinical evaluation

2018 ◽  
Vol 106 (3) ◽  
pp. 229-238 ◽  
Author(s):  
M. H. Sanad ◽  
Alhussein A. Ibrahim
Keyword(s):  
Reaction Time ◽  
Brain Imaging ◽  
In Silico ◽  
Radiochemical Purity ◽  
Biological Evaluation ◽  
Preclinical Evaluation ◽  
Biodistribution Studies ◽  
In Silico Study ◽  
Substrate Ph

AbstractIn the present work, [99mTc]N-histamine has been labeled using [99mTc≡N]2+core. Factors such as, amount of substrate, pH, reaction temperature,in vitrostability and reaction time, have been systematically studied to optimize high radiochemical purity (>99±0.3). Biodistribution studies indicate the suitability of [99mTc]N-histamine as a novel tracer to image brain. The complex of [99mTc]N-histamine may be considered a highly selective radiotracer for brain imaging.

scholarly journals In silico study of lutein as anti-HER-2 receptors in breast cancer treatment

2021 ◽  
Vol 1 (1) ◽  
pp. 17
Author(s):  
Ni Ketut Nitya Cahyani ◽  
Wahyu Nadi Eka Putri ◽  
I Kadek Diva Dwivayana ◽  
Ni Putu Dinda Mirayanti ◽  
Ni Putu Linda Laksmiani
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Binding Energy ◽  
Cancer Progression ◽  
In Silico ◽  
Mechanism Of Inhibition ◽  
Docking Protocol ◽  
In Silico Study ◽  
Her 2 ◽  
In Silico Molecular Docking

Human Epidermal Receptor-2 (HER-2) overexpression is implicated in breast cancer progression; thus, HER-2 is widely used as the target of anticancer therapy. Lapatinib is a drug widely used to inhibit the HER-2 receptor and tyrosine kinase; however, it develops drug resistance. Lutein is promising to be developed as breast cancer therapy. This study aims to determine the mechanism of inhibition of HER-2 receptor overexpression by lutein in silico. Molecular docking was carried out by optimizing the lutein and lapatinib, preparing of protein target HER-2 (PDB ID 3PP0), validating of molecular docking protocol, and docking of lutein and lapatinib on HER-2. The study resulted in the binding energy of -12.37 kcal/mol, while the binding energy of the native ligand and lapatinib to HER-2 was -10.43 kcal/mol and -12.25 kcal/mol, respectively. The binding energy showed that lutein has potential as breast anticancer suggested from the stronger affinity to HER2.

scholarly journals Molecular Docking Study of drug molecules from Drug Bank database against COVID-19 Mpro protein

2020 ◽  
Author(s):  
Tushar Joshi ◽  
Shalini Mathpal ◽  
Priyanka Sharma ◽  
Tanuja Joshi ◽  
Hemlata Pundir ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Drug Repurposing ◽  
Economic Loss ◽  
Docking Study ◽  
New Drugs ◽  
High Morbidity ◽  
Molecular Docking Study ◽  
Drug Molecules ◽  
Therapeutic Development

Aims: SARS-CoV-2 which is NovelCoronavirushas been disseminated all over the world and causing Coronavirus disease (COVID-19) resulting in many deaths as well as economic loss in several countries.This virus is showinga considerable amount of high morbidity and mortality.Currently, no drugs are available againstSARS-CoV-2. Therefore,for the treatment of disease, researchers are looking fornew drugs that can treat the disease and prevent it to be spread.In this regard,drug repurposingmay help scientists for treating and preventing infections associated with SARS-CoV-2. Drug repurposingis a strategy that can identify new targets for existing drugs that are already approved for the treatment of a disease.Main methods: In this study, we present a virtual screening procedure employing deep lerning regression method in 9101 drugs from Drug bank database against the target Main protease (Mpro) for the treatment of COVID-19. 500 screened compounds were subjected to docking.Key findings: Among those 500 drugs, 10 best drugs were selected, which had better binding energy as compared to the reference molecule. Based on the Binding energy score, we can suggest that the identified drug may be considered for therapeutic development against the virus.Significance: Drug repurposing has many advantages as it could shorten the time and reduce the cost of new drug discovery. This research will help to get new drugs against COVID-19 and help humans against this pandemic disease. Keyword- Drug Repurposing, Deep learning, Molecular Docking, COVID-19, Drug bank database, MPro

scholarly journals Bio-Mechanism of Catechin as Pheromone Signal Inhibitor: Prediction of Antibacterial Agent Action Mode by In Vitro and In Silico Study

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6381
Author(s):  
Dikdik Kurnia ◽  
Zenika Febian Ramadhanty ◽  
Aprilina Mora Ardani ◽  
Achmad Zainuddin ◽  
Hendra Dian Adhita Dharsono ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Binding Energy ◽  
Serine Protease ◽  
In Silico ◽  
Antibacterial Agent ◽  
Antibacterial Agents ◽  
Chemical Structures ◽  
In Silico Study ◽  
And Control

The utilization of medicinal plants has long been explored for the discovery of antibacterial agents and the most effective mechanisms or new targets that can prevent and control the spread of antibiotic resistance. One kind of bacterial cell wall inhibition is the inactivation of the MurA enzyme that contributes to the formation of peptidoglycan. Another approach is to interfere with the cell–cell communication of bacteria called the Quorum sensing (QS) system. The blocking of auto-inducer such as gelatinase biosynthesis-activating pheromone (GBAP) can also suppress the virulence factors of gelatinase and serine protease. This research, in particular, aims to analyze lead compounds as antibacterial and anti-QS agents from Gambir (Uncaria gambir Roxburgh) through protein inhibition by in silico study. Antibacterial agents were isolated by bioactivity-guided isolation using a combination of chromatographic methods, and their chemical structures were determined by spectroscopic analysis methods. The in vitro antibacterial activity was evaluated by disc diffusion methods to determine inhibitory values. Meanwhile, in the in silico analysis, the compound of Uncaria gambir was used as ligand and compared with fosfomycin, ambuic acid, quercetin, and taxifolin as the standard ligand. These ligands were attached to MurA, GBAP, gelatinase, and serine proteases using Autodock Vina in PyRx 0.8 followed by PYMOL for combining the ligand conformation and proteins. plus programs to explore the complex, and visualized by Discovery Studio 2020 Client program. The antibacterial agent was identified as catechin that showed inhibitory activity against Enterococcus faecalis ATCC 29212 with inhibition zones of 11.70 mm at 10%, together with MIC and MBC values of 0.63 and 1.25 μg/mL, respectively. In the in silico study, the molecular interaction of catechin with MurA, GBAP, and gelatinase proteins showed good binding energy compared with two positive controls, namely fosfomycin and ambuic acid. It is better to use catechin–MurA (−8.5 Kcal/mol) and catechin–gelatinase (−7.8 Kcal/mol), as they have binding energies which are not marginally different from quercetin and taxifolin. On the other hand, the binding energy of serine protease is lower than quercetin, taxifolin, and ambuic acid. Based on the data, catechin has potency as an antibacterial through the inhibition of GBAP proteins, gelatinase, and serine protease that play a role in the QS system. This is the first discovery of the potential of catechin as an alternative antibacterial agent with an effective mechanism to prevent and control oral disease affected by antibiotic resistance.

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