Estimation of Binding Sites of Efavirenz with 3EO9 Receptor: In Silico Molecular Docking and Molecular Dynamics Studies

In this work, Andrographis paniculata compounds of Andrographolide, Neoandrographolide, and 5-hydroxy-7,8,2’,3’-tetramethoxyflavone inhibition activity to SARS CoV-2 main protease were examined through in silico molecular docking and molecular dynamics simulation, with Remdesivir as control ligand. Docking score and MMGBSA were examined as well as molecular dynamics parameters: RMSD, RMSF and Protein ligand contact fraction. Our study found that Andrographis paniculata compounds of Andrographolide, Neoandrographolide, and 5-hydroxy-7,8,2’,3’-tetramethoxyflavone have comparable inhibition activity to SARS CoV-2 main protease in comparison to Remdesivir. 5-hydroxy7,8,2’,3’-tetramethoxyflavone has the lowest docking score, which was further validated by protein ligand contact fraction examination, although MMGBSA score is lowest for Remdesivir.

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The Antiviral and Antimalarial Drug Repurposing in Quest of Chemotherapeutics to Combat COVID-19 Utilizing Structure-Based Molecular Docking

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323999200824115536 ◽

2020 ◽

Vol 23 ◽

Author(s):

Sisir Nandi ◽

Mohit Kumar ◽

Mridula Saxena ◽

Anil Kumar Saxena

Keyword(s):

Molecular Docking ◽

In Silico ◽

Drug Repurposing ◽

Clinical Settings ◽

The Novel ◽

In Silico Docking ◽

Biochemical Mechanisms ◽

Novel Coronavirus ◽

In Silico Molecular Docking

Background: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted in the quest of the medicine that can cure COVID- 19. Objective: Existing antivirals such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine have been repurposed to fight the current coronavirus epidemic. But exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. Method: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs including antivirals and antimalarials to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. Results: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. Conclusion: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.

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Promising Anti-stroke Signature of Voglibose: Investigation through In- Silico Molecular Docking and Virtual Screening in In-Vivo Animal Studies

Current Gene Therapy ◽

10.2174/1566523220999200726225457 ◽

2020 ◽

Vol 20 (3) ◽

pp. 223-235

Author(s):

Pooja Shah ◽

Vishal Chavda ◽

Snehal Patel ◽

Shraddha Bhadada ◽

Ghulam Md. Ashraf

Keyword(s):

Molecular Docking ◽

Virtual Screening ◽

In Silico ◽

Reductase Activity ◽

Infarct Volume ◽

Docking Studies ◽

Serum Glucose ◽

In Vivo Studies ◽

In Silico Molecular Docking

Background: Postprandial hyperglycemia considered to be a major risk factor for cerebrovascular complications. Objective: The current study was designed to elucidate the beneficial role of voglibose via in-silico in vitro to in-vivo studies in improving the postprandial glycaemic state by protection against strokeprone type 2 diabetes. Material and Methods: In-Silico molecular docking and virtual screening were carried out with the help of iGEMDOCK+ Pymol+docking software and Protein Drug Bank database (PDB). Based on the results of docking studies, in-vivo investigation was carried out for possible neuroprotective action. T2DM was induced by a single injection of streptozotocin (90mg/kg, i.v.) to neonates. Six weeks after induction, voglibose was administered at the dose of 10mg/kg p.o. for two weeks. After eight weeks, diabetic rats were subjected to middle cerebral artery occlusion, and after 72 hours of surgery, neurological deficits were determined. The blood was collected for the determination of serum glucose, CK-MB, LDH and lipid levels. Brains were excised for determination of brain infarct volume, brain hemisphere weight difference, Na+-K+ ATPase activity, ROS parameters, NO levels, and aldose reductase activity. Results: In-silico docking studies showed good docking binding score for stroke associated proteins, which possibly hypotheses neuroprotective action of voglibose in stroke. In the present in-vivo study, pre-treatment with voglibose showed a significant decrease (p<0.05) in serum glucose and lipid levels. Voglibose has shown significant (p<0.05) reduction in neurological score, brain infarct volume, the difference in brain hemisphere weight. On biochemical evaluation, treatment with voglibose produced significant (p<0.05) decrease in CK-MB, LDH, and NO levels in blood and reduction in Na+-K+ ATPase, oxidative stress, and aldose reductase activity in brain homogenate. Conclusion: In-silico molecular docking and virtual screening studies and in-vivo studies in MCAo induced stroke, animal model outcomes support the strong anti-stroke signature for possible neuroprotective therapeutics.

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In Silico Molecular Docking and Interaction Analysis of Traditional Chinese Medicines Against SARS-CoV-2 Receptor

Natural Product Communications ◽

10.1177/1934578x211015030 ◽

2021 ◽

Vol 16 (5) ◽

pp. 1934578X2110150

Author(s):

Gang Li ◽

Wei Zhou ◽

Xiurong Zhao ◽

Ying Xie

Keyword(s):

Molecular Docking ◽

In Silico ◽

Interaction Analysis ◽

Herbal Remedies ◽

Receptor Protein ◽

Stable Complex ◽

Traditional Chinese Medicines ◽

Ligand Interaction ◽

Chinese Medicines ◽

In Silico Molecular Docking

The novel coronavirus, 2019-nCoV, has led to a major pandemic in 2020 and is responsible for more than 2.9 million officially recorded deaths worldwide. As well as synthetic anti-viral drugs, there is also a need to explore natural herbal remedies. The Traditional Chinese Medicines (TCMs) system has been used for thousands of years for the prevention, diagnosis, and treatment of several chronic diseases. In this paper, we performed an in silico molecular docking and interaction analysis of TCMs against SARS-CoV-2 receptor RNA-dependent RNA polymerase (RdRp). We obtained the 5 most effective plant compounds which had a better binding affinity towards the target receptor protein. These compounds areforsythoside A, rutin, ginkgolide C, icariside II, and nolinospiroside E. The top-ranked compound, based on docking score, was nolinospiroside, a glycoside found in Ophiopogon japonicas that has antioxidant properties. Protein-ligand interaction analysis discerned that nolinospiroside formed a strong bond between ARG 349 of the protein receptor and the carboxylate group of the ligand, forming a stable complex. Hence, nolinospiroside could be deployed as a lead compound against SARS-CoV-2 infection that can be further investigated for its potential benefits in curbing the viral infection.

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Structural insights from an in silico molecular docking simulation of complement component 3a receptor 1 with an antagonist

Journal of Molecular Graphics and Modelling ◽

10.1016/j.jmgm.2021.107914 ◽

2021 ◽

pp. 107914

Author(s):

Kensuke Misawa ◽

Yoshiya Sugai ◽

Taketoshi Fujimori ◽

Takatsugu Hirokawa

Keyword(s):

Molecular Docking ◽

In Silico ◽

Docking Simulation ◽

Complement Component ◽

Molecular Docking Simulation ◽

In Silico Molecular Docking ◽

Structural Insights

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Study of Endogen Substrates, Drug Substrates and Inhibitors Binding Conformations on MRP4 and Its Variants by Molecular Docking and Molecular Dynamics

Molecules ◽

10.3390/molecules26041051 ◽

2021 ◽

Vol 26 (4) ◽

pp. 1051

Author(s):

Edgardo Becerra ◽

Giovanny Aguilera-Durán ◽

Laura Berumen ◽

Antonio Romo-Mancillas ◽

Guadalupe García-Alcocer

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Binding Energy ◽

Binding Site ◽

Binding Sites ◽

Adenosine Monophosphate ◽

Competitive Inhibitor ◽

Umbrella Sampling ◽

Coarse Grained ◽

Nucleotide Polymorphisms

Multidrug resistance protein-4 (MRP4) belongs to the ABC transporter superfamily and promotes the transport of xenobiotics including drugs. A non-synonymous single nucleotide polymorphisms (nsSNPs) in the ABCC4 gene can promote changes in the structure and function of MRP4. In this work, the interaction of certain endogen substrates, drug substrates, and inhibitors with wild type-MRP4 (WT-MRP4) and its variants G187W and Y556C were studied to determine differences in the intermolecular interactions and affinity related to SNPs using protein threading modeling, molecular docking, all-atom, coarse grained, and umbrella sampling molecular dynamics simulations (AA-MDS and CG-MDS, respectively). The results showed that the three MRP4 structures had significantly different conformations at given sites, leading to differences in the docking scores (DS) and binding sites of three different groups of molecules. Folic acid (FA) had the highest variation in DS on G187W concerning WT-MRP4. WT-MRP4, G187W, Y556C, and FA had different conformations through 25 ns AA-MD. Umbrella sampling simulations indicated that the Y556C-FA complex was the most stable one with or without ATP. In Y556C, the cyclic adenosine monophosphate (cAMP) and ceefourin-1 binding sites are located out of the entrance of the inner cavity, which suggests that both cAMP and ceefourin-1 may not be transported. The binding site for cAMP and ceefourin-1 is quite similar and the affinity (binding energy) of ceefourin-1 to WT-MRP4, G187W, and Y556C is greater than the affinity of cAMP, which may suggest that ceefourin-1 works as a competitive inhibitor. In conclusion, the nsSNPs G187W and Y556C lead to changes in protein conformation, which modifies the ligand binding site, DS, and binding energy.

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α-Aminophosphonates 4-XC6H4–NH–CH(4-BrC6H4)–P(O)(OiPr)2 (X = H, Br, MeO): Crystal structures, Hirshfeld surface analysis, computational studies and in silico molecular docking with the SARS-CoV-2 proteins

Tetrahedron ◽

10.1016/j.tet.2021.132376 ◽

2021 ◽

pp. 132376

Author(s):

Larisa E. Alkhimova ◽

Maria G. Babashkina ◽

Damir A. Safin

Keyword(s):

Molecular Docking ◽

Crystal Structures ◽

Surface Analysis ◽

In Silico ◽

Hirshfeld Surface ◽

Hirshfeld Surface Analysis ◽

Computational Studies ◽

In Silico Molecular Docking

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In silico molecular docking and in vitro antimicrobial efficacy of phytochemicals against multi-drug-resistant enteroaggregative Escherichia coli and non-typhoidal Salmonella spp.

Gut Pathogens ◽

10.1186/s13099-021-00443-3 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Padikkamannil Abishad ◽

Pollumahanti Niveditha ◽

Varsha Unni ◽

Jess Vergis ◽

Nitin Vasantrao Kurkure ◽

...

Keyword(s):

Escherichia Coli ◽

Molecular Docking ◽

In Silico ◽

Docking Studies ◽

Antimicrobial Efficacy ◽

Drug Resistant ◽

Protein Motifs ◽

Phytochemical Compounds ◽

In Silico Molecular Docking

Abstract Background In the wake of emergence of antimicrobial resistance, bioactive phytochemical compounds are proving to be important therapeutic agents. The present study envisaged in silico molecular docking as well as in vitro antimicrobial efficacy screening of identified phytochemical ligands to the dispersin (aap) and outer membrane osmoporin (OmpC) domains of enteroaggregative Escherichia coli (EAEC) and non-typhoidal Salmonella spp. (NTS), respectively. Materials and methods The evaluation of drug-likeness, molecular properties, and bioactivity of the identified phytocompounds (thymol, carvacrol, and cinnamaldehyde) was carried out using Swiss ADME, while Protox-II and StopTox servers were used to identify its toxicity. The in silico molecular docking of the phytochemical ligands with the protein motifs of dispersin (PDB ID: 2jvu) and outer membrane osmoporin (PDB ID: 3uu2) were carried out using AutoDock v.4.20. Further, the antimicrobial efficacy of these compounds against multi-drug resistant EAEC and NTS strains was determined by estimating the minimum inhibitory concentrations and minimum bactericidal concentrations. Subsequently, these phytochemicals were subjected to their safety (sheep and human erythrocytic haemolysis) as well as stability (cationic salts, and pH) assays. Results All the three identified phytochemicals ligands were found to be zero violators of Lipinski’s rule of five and exhibited drug-likeness. The compounds tested were categorized as toxicity class-4 by Protox-II and were found to be non- cardiotoxic by StopTox. The docking studies employing 3D model of dispersin and ompC motifs with the identified phytochemical ligands exhibited good binding affinity. The identified phytochemical compounds were observed to be comparatively stable at different conditions (cationic salts, and pH); however, a concentration-dependent increase in the haemolytic assay was observed against sheep as well as human erythrocytes. Conclusions In silico molecular docking studies provided useful insights to understand the interaction of phytochemical ligands with protein motifs of pathogen and should be used routinely before the wet screening of any phytochemicals for their antibacterial, stability, and safety aspects.

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