scholarly journals HIGH-THROUGHPUT SCREENING AND DYNAMIC STUDIES OF SELECTED COMPOUNDS AGAINST SARS-COV-2

2022 ◽  
pp. 251-260
Author(s):  
RATUL BHOWMIK ◽  
RANAJIT NATH ◽  
SAMEER SHARMA ◽  
RATNA ROY ◽  
RIYA BISWAS
Keyword(s):  
Drug Delivery ◽  
Molecular Docking ◽  
Binding Affinity ◽  
High Throughput Screening ◽  
In Silico Analysis ◽  
Inhibitory Effect ◽  
Binding Affinities ◽  
Pubchem Database ◽  
Potential Inhibitors ◽  
3Cl Protease

Objective: This study was aimed to analyze the inhibitory effect of the drugs used in nanocarrier as well as nanoparticles formulation based drug delivery system selected from PubChem database literature against 3CLpro (3C-like protease) receptor of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) by implementing several in silico analysis techniques. Methods: This paper detailed a molecular docking-based virtual screening of 5240 compounds previously utilized in nanoparticle and nanocarrier drug delivery systems utilizing AutoDock Vina software on 3CL protease to discover potential inhibitors using a molecular docking technique. Results: According to the results of the screening, the top two compounds, PubChem Id 58823276 and PubChem Id 60838 exhibited a high affinity for the 3CL protease binding region. Their binding affinities were-9.6 and-8.5 kJ/mol, indicating that they were tightly bound to the target receptor, respectively. These results outperformed those obtained using the co-crystallized native ligand, which exhibited a binding affinity of-7.4 kJ/mol. PubChem Id 60838, the main hit compound in terms of both binding affinity and ADMET analysis, displayed substantial deformability after MD simulation. As a result of the VS and molecular docking techniques, novel 3CL protease inhibitors from the PubChem database were discovered using the Lipinski rule of five and functional molecular contacts with the target protein, as evidenced by the findings of this work. Conclusion: The findings suggest that the compounds discovered may represent attractive opportunities for the development of COVID-19 3CLpro inhibitors and that they need further evaluation and investigation.

scholarly journals Study of Baicalin toward COVID-19 Treatment: In silico Target Analysis and in vitro Inhibitory Effects on SARS-CoV-2 Proteases

2021 ◽  
pp. 122-137
Author(s):  
Chingju Lin ◽  
Fuu-Jen Tsai ◽  
Yuan-Man Hsu ◽  
Tsung-Jung Ho ◽  
Guo-Kai Wang ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Pathway Analysis ◽  
Acute Inflammation ◽  
Inhibitory Effect ◽  
Pharmacological Effects ◽  
Inhibitory Effects ◽  
Rna Dependent Rna Polymerase ◽  
Negative Impacts

Negative impacts of COVID-19 on human health and economic and social activities urge scientists to develop effective treatments. Baicalin is a natural flavonoid, extracted from a traditional medicinal plant, previously reported with anti-inflammatory activity. In this study, we used pharmacophore fitting and molecular docking to screen and determine docking patterns and the binding affinity of baicalin on 3 major targets of SARS-CoV-2 (3-chymotrypsin-like cysteine protease [3CLpro], papain-like protease [PLpro], and RNA-dependent RNA polymerase). The obtained data revealed that baicalin has high pharmacophore fitting on 3CLpro and predicted good binding affinity on PLpro. Moreover, using the enzymatic assay, we examined the inhibitory effect of baicalin in vitro on the screened enzymes. Baicalin also exhibits inhibitory effect on these proteases in vitro. Additionally, we performed pharmacophore-based screening of baicalin on human targets and conducted pathway analysis to explore the potential cytoprotective effects of baicalin in the host cell that may be beneficial for COVID-19 treatment. The result suggested that baicalin has multiple targets in human cell that may induce multiple pharmacological effects. The result of pathway analysis implied that these targets may be associated with baicalin-induced bioactivities that are involved with signals of pro-inflammation factors, such as cytokine and chemokine. Taken together with supportive data from the literature, the bioactivities of bailalin may be beneficial for COVID-19 treatment by reducing cytokine-induced acute inflammation. In conclusion, baicalin is potentially a good candidate for developing new therapeutic to treat COVID-19.

Prediction Mechanism of Nevadensin as Antibacterial Agent against S. sanguinis: In vitro and In silico Studies

2021 ◽  
Vol 24 ◽  
Author(s):  
Aldina Amalia Nur Shadrina ◽  
Yetty Herdiyati ◽  
Ika Wiani ◽  
Mieke Hemiawati Satari ◽  
Dikdik Kurnia
Keyword(s):  
Antibacterial Activity ◽  
Molecular Docking ◽  
Dental Caries ◽  
Binding Affinity ◽  
In Silico ◽  
Antibacterial Agent ◽  
In Silico Analysis ◽  
Dna Gyrase ◽  
Silico Analysis

Background: Streptococcus sanguinis can contribute to tooth demineralization, which can lead to dental caries. Antibiotics used indefinitely to treat dental caries can lead to bacterial resistance. Discovering new antibacterial agents from natural products like Ocimum basilicum will help combat antibiotic resistance. In silico analysis (molecular docking) can help determine the lead compound by studying the molecular interaction between the drug and the target receptor (MurA enzyme and DNA gyrase). It is a potential candidate for antibacterial drug development. Objective: The research objective is to isolate the secondary metabolite of O. basilicum extract that has activity against S. sanguinis through in vitro and in silico analysis. Methods: n-Hexane extract of O. basilicum was purified by combining column chromatography with bioactivity-guided. The in vitro antibacterial activity against S. sanguinis was determined using the disc diffusion and microdilution method, while molecular docking simulation of nevadensin (1) with MurA enzyme and DNA gyrase was performed used PyRx 0.8 program. Results: Nevadensin from O. basilicum was successfully isolated and characterized by spectroscopic methods. This compound showed antibacterial activity against S. sanguinis with MIC and MBC values of 3750 and 15000 μg/mL, respectively. In silico analysis showed that the binding affinity to MurA was -8.5 Kcal/mol, and the binding affinity to DNA gyrase was -6.7 Kcal/mol. The binding of nevadensin-MurA is greater than fosfomycin-MurA. Otherwise, Nevadensin-DNA gyrase has a weaker binding affinity than fluoroquinolone-DNA gyrase and chlorhexidine-DNA gyrase. Conclusion: Nevadensin showed potential as a new natural antibacterial agent by inhibiting the MurA enzyme rather than DNA gyrase.

scholarly journals Design of more potent quinazoline derivatives as EGFRWT inhibitors for the treatment of NSCLC: a computational approach

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Muhammad Tukur Ibrahim ◽  
Adamu Uzairu ◽  
Sani Uba ◽  
Gideon Adamu Shallangwa
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Binding Affinity ◽  
Positive Control ◽  
Computational Approach ◽  
Tyrosine Kinase Receptor ◽  
Binding Affinities ◽  
Binding Interaction ◽  
Pharmacokinetic Properties ◽  
Inhibitory Activities

Abstract Background Lung cancer remains the leading and deadly type of cancer worldwide. It was estimated to account for about 25% of the 7 million people that died as a result of cancer-related issues/mortality every year in the world. Non-small cell lung cancer (NSCLC) is the lethal/deadly class of lung cancer with nearly 1.5 million reported cases and less than 20% survival rate. Therefore, it becomes necessary to explore more effective NSCLC drugs. Result A computational approach was employed here to design ten new EGFRWT inhibitors using compound 18 as a template for the design identified with the best binding affinity and good pharmacokinetic properties previously reported in our work. The modeled inhibitory activities of these newly designed EGFRWT inhibitors (range from 7.746966 to 11.09261) were better than that of the hit compound with pIC50 of 7.5639 and gefitinib the positive control with pIC50 of 5.879426. The ligand-binding interaction between these newly designed EGFRWT inhibitors and the EGFR tyrosine kinase receptor as shown in Table 3 was investigated and elucidated using molecular docking protocol. Based on the molecular docking results, the binding affinities of these newly designed EGFRWT inhibitors were found to be between − 8.8 and − 9.5 kcal/mol. The designed compound SFD10 has the highest binding affinity of − 9.5 kcal/mol followed by compound SFD8 (with a binding affinity of − 9.3 kcal/mol), then by compound SFD9 and 4 (each with a binding affinity of − 9.3 kcal/mol). None of them was found to have more than one violation of the filtering criterion used in this study thereby showing good ADMET properties. Conclusion The modeled inhibitory activities and binding affinities of these newly designed EGFRWT inhibitors were found to be higher than that of the template compound and the control (gefitinib) used in this research. They were also seen to be non-toxic with good pharmacokinetic properties.

scholarly journals Molecular Docking Analysis Of Some Phytochemicals On Two SARS-CoV-2 Targets: Potential Lead Compounds Against Two Target Sites of SARS-CoV-2 Obtained from Plants

2020 ◽  
Author(s):  
Amaka Ubani ◽  
Francis Agwom ◽  
Oluwatoyin RuthMorenikeji ◽  
Shehu Nathan ◽  
Pam Luka ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Potential Candidate ◽  
Binding Affinities ◽  
Protein Targets ◽  
Docking Analysis ◽  
Lead Compounds ◽  
Target Sites ◽  
Antiviral Activities ◽  
Molecular Docking Analysis

AbstractCOV spike (S) glycoprotein and Mpro are two key targets that have been identified for vaccines and drug development against the COVID-19 disease. Virtual screening of some compounds of plants origin that have shown antiviral activities were carried out on the two targets, 6lu7 and 6vsb by docking with the PyRx software. The binding affinities were compared with other compounds and drugs already identified as potential ligands for 6lu7 and 6vsb as well as Chloroquine and hydroxychloroquine. The docked compounds with best binding affinities were also filtered for drug likeness using the SwissADME and PROTOX platforms on the basis of Physicochemical properties and toxicity respectively. The docking results revealed that scopodulcic acid and dammarenolic acid had the best binding affinity on the s-glycoprotein and Mpro protein targets respectively. Silybinin also demonstrated a good binding affinity to both protein targets making it a potential candidate for further evaluation as repurposed candidate for SARS COV2 with likelihood of having a multitarget activity.

scholarly journals Computational Molecular Docking and Virtual Screening Revealed Promising SARS-CoV-2 Drugs

2020 ◽  
Author(s):  
Maryam Hosseini ◽  
Wanqiu Chen ◽  
Charles Wang
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Virtual Screening ◽  
Clinical Studies ◽  
Inhibitory Effect ◽  
Docking Approach ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Potential Inhibitors ◽  
Computational Molecular Docking

The pandemic of novel coronavirus disease 2019 (COVID-19) is rampaging the world with more than 1.4 million of confirmed cases and more than 85,000 of deaths across world by April 9th, 2020. There is an urgent need to identify effective drugs to fight against the virus. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the family of coronaviruses consisting of four structural and 16 non-structured proteins. Three non-structural proteins such as main protease, papain like protease, and RNA-dependent RNA polymerase are believed to play a crucial role in the virus replication. We applied a computational ligand-receptor binding modeling and performed a comprehensive virtual screening on the FDA-approved drugs against these three SARS-CoV-2 proteins using AutoDock Vina. Our computational studies indicated that Simeprevir, Ledipasvir, Idarubicin, Saquinavir, Ledipasivir, Partitaprevir, Glecaprevir, and Velpatasvir are all promising inhibitors, which displayed a lower binding energy (higher inhibitory effect) than Remdesivir, Lopinavir, and Ritonavir. However, we found that chloroquine and hydroxychloroquine, which showed efficacy in treating the COVID-19 in recent clinical studies, had high binding energy with all three proteins, suggesting they may work through a different mechanism. We also identified several novel drugs as potential inhibitors against SARS-CoV-2, including antiviral Raltegravir; antidiabetic Amaryl; antibiotics Retapamulin, Rifimixin, and Rifabutin; antiemetic Fosaprepitant and Netupitant. In summary, our computational molecular docking approach and virtual screening identified some promising candidate SARS-CoV-2 drugs that may be considered for further clinical studies.

scholarly journals IDENTIFICATION OF POSSIBLE MOLECULAR TARGETS OF POTENTIAL ANTI-PARKINSON DRUGS BY PREDICTING THEIR BINDING AFFINITIES USING MOLECULAR DOCKING TECHNIQUE

2018 ◽  
Vol 11 (14) ◽  
pp. 28
Author(s):  
Maguemga Homsi Chanceline Dorice ◽  
Navneet Khurana ◽  
Neha Sharma ◽  
Gopal L Khatik
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Energy Minimization ◽  
Molecular Targets ◽  
Mechanistic Study ◽  
Binding Affinities ◽  
Autodock Vina ◽  
3D Structures ◽  
Mao B ◽  
3D Software

Objective: Mechanistic study of newly reported anti-Parkinson agents by molecular docking to predict possible target.Methods: Structures of newer drugs known anti-Parkinson agents were drawn using ChemBioDraw 2D software. Thereafter, they were converted to 3D structures using ChemBioDraw 3D software in which they were subjected to energy minimization using the MM2 method and then saved as PDB extension files, which can be accessed using the AutoDock Vina (ADT) interface. ADT 1.5.6 software version was used for molecular docking study.Results: Various molecular targets were selected (D2/D3, D2, A2A, and MAO-B) and studied for Pardoprunox, Istradefylline, Rasagiline, and Bromocriptine. Pardoprunox, Istradefylline, and Bromocriptine had more affinity with their corresponding receptor with −6.9, −8.5, and −9.4 kcal/mol binding affinity, respectively, except Rasagiline, who has less affinity with its corresponding receptor (−6.4kcal/mol) and shown better affinity with 3pbl receptor (−6.7 kcal/mol).Conclusion: Pardoprunox, Istradefylline, and Bromocriptine were found to act on D2/D3 (3pbl), A2A (3pwh), and D2 (4yyw), respectively, whereas Rasagiline found to be act on D2/D3 (3pbl) receptor. The results help in prediction of mechanism and interaction to various Parkinson’s disease targets.

scholarly journals Chemical Profiles and Pharmacological Properties with in Silico Studies on Elatostema papillosum Wedd

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 809 ◽  
Author(s):  
Md. Zia Uddin ◽  
Arkajyoti Paul ◽  
Ahmed Rakib ◽  
Saad Ahmed Sami ◽  
Shafi Mahmud ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Serotonin Receptor ◽  
Computational Study ◽  
Biological Activities ◽  
Binding Affinities ◽  
In Silico Studies ◽  
Cox 2 ◽  
Cox 1

The current study attempted, for the first time, to qualitatively and quantitatively determine the phytochemical components of Elatostema papillosum methanol extract and their biological activities. The present study represents an effort to correlate our previously reported biological activities with a computational study, including molecular docking, and ADME/T (absorption, distribution, metabolism, and excretion/toxicity) analyses, to identify the phytochemicals that are potentially responsible for the antioxidant, antidepressant, anxiolytic, analgesic, and anti-inflammatory activities of this plant. In the gas chromatography-mass spectroscopy analysis, a total of 24 compounds were identified, seven of which were documented as being bioactive based on their binding affinities. These seven were subjected to molecular docking studies that were correlated with the pharmacological outcomes. Additionally, the ADME/T properties of these compounds were evaluated to determine their drug-like properties and toxicity levels. The seven selected, isolated compounds displayed favorable binding affinities to potassium channels, human serotonin receptor, cyclooxygenase-1 (COX-1), COX-2, nuclear factor (NF)-κB, and human peroxiredoxin 5 receptor proteins. Phytol acetate, and terpene compounds identified in E. papillosum displayed strong predictive binding affinities towards the human serotonin receptor. Furthermore, 3-trifluoroacetoxypentadecane showed a significant binding affinity for the KcsA potassium channel. Eicosanal showed the highest predicted binding affinity towards the human peroxiredoxin 5 receptor. All of these findings support the observed in vivo antidepressant and anxiolytic effects and the in vitro antioxidant effects observed for this extract. The identified compounds from E. papillosum showed the lowest binding affinities towards COX-1, COX-2, and NF-κB receptors, which indicated the inconsequential impacts of this extract against the activities of these three proteins. Overall, E. papillosum appears to be bioactive and could represent a potential source for the development of alternative medicines; however, further analytical experiments remain necessary.

scholarly journals Molecular docking analysis of selected phytochemicals on two SARS-CoV-2 targets

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1157
Author(s):  
Amaka Ubani ◽  
Francis Agwom ◽  
Oluwatoyin Ruth Morenikeji ◽  
Nathan Yakubu Shehu ◽  
Emmanuel Arinze Umera ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Drug Formulation ◽  
Potential Candidate ◽  
Binding Affinities ◽  
Plant Origin ◽  
Protein Targets ◽  
Docking Analysis ◽  
Antiviral Activities

Background: The coronavirus spike (S) glycoprotein and M protease are two key targets that have been identified for vaccines and drug development against COVID-19. Methods: Virtual screening of some compounds of plant origin that have shown antiviral activities were carried out on the two targets, the M protease (PDB ID 6LU7) and S glycoprotein (PDB ID 6VSB), by docking with PyRx software. The binding affinities were compared with other compounds and drugs already identified as potential ligands for the M protease and S glycoprotein, as well as chloroquine and hydroxychloroquine. The docked compounds with best binding affinities were also filtered for drug likeness using the SwissADME and PROTOX platforms on the basis of physicochemical properties and toxicity, respectively. Results: The docking results revealed that scopadulcic acid and dammarenolic acid had the best binding affinity for the S glycoprotein and Mpro protein targets, respectively. Silybinin, through molecular docking, also demonstrated good binding affinity for both protein targets making it a potential candidate for further evaluation as repurposed candidate for SARS-CoV-2, with likelihood of having multitarget activity as it showed activities for both targets. Conclusions: The study proposes that scopadulcic acid and dammarenolic acid be further evaluated in vivo for drug formulation against SARS-COV-2 and possible repurposing of Silybinin for the management of COVIV-19.

Sign in / Sign up

Export Citation Format

Share Document