Theaflavin-3’-O-gallate a Black-tea Constituent Blocked SARS CoV-2 RNA dependant RNA Polymerase Active-site with Better Docking Results than Remdesivir

Drug Research ◽  
2021 ◽  
Author(s):  
Amrita Banerjee ◽  
Mehak Kanwar ◽  
Smarajit Maiti
Keyword(s):  
Binding Energy ◽  
Rna Polymerase ◽  
Black Tea ◽  
Antiviral Effect ◽  
Docking Study ◽  
Inhibitory Effect ◽  
Cation Binding ◽  
Molecular Docking Study ◽  
Entry Site ◽  
Cation Binding Site

Abstract Background Replication of SARS-CoV-2 depends on viral RNA-dependent RNA-polymerase (RdRp). Remdesivir, the broad-spectrum RdRp inhibitor acts as nucleoside-analogues (NAs). Remdesivir has initially been repurposed as a promising drug against SARS-CoV-2 infection with some health hazards like liver damage, allergic reaction, low blood-pressure, and breathing-shortness, throat-swelling. In comparison, theaflavin-3’-O-gallate (TFMG), the abundant black tea component has gained importance in controlling viral infection. TFMG is a non-toxic, non-invasive, antioxidant, anticancer and antiviral molecule. Results Here, we analyzed the inhibitory effect of theaflavin-3’-O-gallate on SARS CoV-2 RdRp in comparison with remdesivir by molecular-docking study. TFMG has been shown more potent in terms of lower Atomic-Contact-Energy (ACE) and higher occupancy of surface area; −393.97 Kcal/mol and 771.90 respectively, favoured with lower desolvation-energy; −9.2 Kcal/mol. TFMG forms more rigid electrostatic and H-bond than remdesivir. TFMG showed strong affinity to RNA primer and template and RNA passage-site of RdRp. Conclusions TFMG can block the catalytic residue, NTP entry site, cation binding site, nsp7-nsp12 junction with binding energy of −6. 72 Kcal/mol with Ki value of 11.79, and interface domain with binding energy of −7.72 and −6.16 Kcal/mol with Ki value of 2.21 and 30.71 µM. And most importantly, TFMG shows antioxidant/anti-inflammatory/antiviral effect on human studies.

Molecular Docking Study for Analyzing the Inhibitory Effect of Anti-inflammatory Plant Compound Against Tumour Necrosis Factor (TNF-α)

2019 ◽  
Vol 14 (1) ◽  
pp. 85-90
Author(s):  
Sagarika Biswas
Keyword(s):  
Molecular Docking ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Docking Study ◽  
Developed Countries ◽  
Inhibitory Effect ◽  
Molecular Docking Study ◽  
Drug Designing ◽  
Anti Inflammatory ◽  
Necrosis Factor

Background: Rheumatoid Arthritis (RA) is an autoimmune disorder of symmetric synovial joints which is characterized by the chronic inflammation with 0.5-1% prevalence in developed countries. Presence of persistent inflammation is attributed to the major contribution of key inflammatory cytokine and tumour necrosis factor- alpha (TNF- &#945;). Recent drug designing studies are developing TNF-&#945; blockers to provide relief from the symptoms of the disease such as pain and inflammation. Available blockers are showing certain limitations such as it may enhance the rate of tuberculosis (TB) occurrence, lymphoma risk, cost issues and certain infections are major concern. Discussed limitations implicated a need of development of some alternative drugs which exhibit fewer side effects with low cost. Therefore, we have identified anti-inflammatory compounds in an underutilized fruit of Baccaurea sapida (B.sapida) in our previous studies. Among them quercetin have been identified as the most potent lead compound for drug designing studies of RA. </P><P> Methods: In the present article, characterization of quercetin has been carried out to check its drug likeliness and molecular docking study has been carried out between TNF- &#945; and quercetin by using AutoDock 4.2.1 software. Further, inhibitory effect of B. sapida fruit extract on RA plasma has been analysed through immunological assay ELISA. </P><P> Results: Our in-silico analysis indicated that quercetin showed non carcinogenic reaction in animal model and it may also cross the membrane barrier easily. We have studied the ten different binding poses and best binding pose of TNF-&#945; and quercetin showed -6.3 kcal/mol minimum binding energy and 23.94 &#181;M inhibitory constant. In addition to this, ELISA indicated 2.2 down regulated expression of TNF-&#945; in RA compared to control. </P><P> Conclusion: This study may further be utilized for the drug designing studies to reduce TNF-&#945; mediated inflammation in near future. This attempt may also enhance the utilization of this plant worldwide.

scholarly journals Synthesis and Anticancer Activity Evaluation of Azepinobisindoles; the Isomeric Iheyamine A Derivatives

2019 ◽  
Vol 35 (2) ◽  
pp. 723-731
Author(s):  
Weerachai Phutdhawong ◽  
Sopita Rattanopas ◽  
Jitnapa Sirirak ◽  
Thongchai Taechowisan ◽  
Waya S. Phutdhawong
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Human Cancer ◽  
Docking Study ◽  
Inhibitory Effect ◽  
Molecular Docking Study ◽  
Human Cancer Cell Lines ◽  
Activity Evaluation ◽  
Cancer Line

Azepinobisindole derivatives, the isomeric Iheyamine skeleton, was prepared and its anticancer activity evaluation were investigated against two human cancer cell lines, Hepatocellular carcinoma (HepG2) and human cervical cancer line (Hela) as well as the normal cell line (Vero cell line) using MTT assay. The anticancer activity results indicated that 2-methoxy-5-methyl-5H-azepino[2,3-b:4,5-bʹ]diindole was the most active derivative against tested cell lines. Additionally, molecular docking study in silico the possible inhibitory effect of cyclin-dependent kinase 2 (CDK2) by the azepinoindole revealed that all synthesized compounds fit well in the binding cavity of CDK2.

scholarly journals Molecular docking study of the phytol and its derivatives against COX-2 induced inflammation: A combined density functional study

2020 ◽  
pp. 1-5
Author(s):  
Muhammad Torequl Islam ◽  
Pranta Ray ◽  
Abul Bashar Ripon Khalipha ◽  
SM Hafiz Hassan ◽  
Md. Roich Khan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Density Functional ◽  
Chemical Reactivity ◽  
Docking Study ◽  
Functional Study ◽  
Molecular Docking Study ◽  
Study Results ◽  
Homo And Lumo ◽  
Cox 2

This study aimed to determine the activity of PYT and its derivatives against COX-2, including 5IKR protein induced inflammation by using the computational tools. PYT and its derivatives have been designed by utilizing density functional theory (DFT) and the performance of the drugs was also evaluated by molecular docking study. Results suggest that the NH2 derivative of PYT (D-NH2) showed binding energy -6.4 (Kcal/mol) with protein 5IKR of COX-2 compared to the main drug (D) that showed binding energy -5.1 (Kcal/mol) with the same protein. HOMO and LUMO energy values were also calculated to determine the chemical reactivity of all the modified drugs. Non-covalent interactions of PYT and its derivatives were essential in improving the performance. In conclusion, D-NH2 showed better preference in inhibiting to the protein 5IKR of COX-2 compared to other modified drugs and it can be claimed that D-NH2 will be the best conformer for COX-2 induced inflammation.

scholarly journals Investigation of Anti-Coronavirus, Anti-HCV, Nucleotide Inhibitors, and Bioactive Molecules efficacy Against RNA-directed RNA polymerase of Nipah Virus: Molecular Docking Study

2021 ◽  
Vol 10 (1) ◽  
pp. 78
Author(s):  
Peter T. Habib
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
Nipah Virus ◽  
Docking Study ◽  
The Philippines ◽  
Bioactive Molecules ◽  
World Health ◽  
Energy Estimates ◽  
Molecular Docking Study ◽  
Rna Dependent Rna Polymerase

Introduction: The infections with the Nipah virus (NiV) are highly infectious and may lead to severe febrile encephalitis. High mortality rates in southeastern Asia, including Bengal, Malaysia, Papua New Guinea, Vietnam, Cambodia, Indonesia, Madagascar, the Philippines, Thailand, and India, have been reported in NiV outbreaks. Considering the high risk of an epidemic, NiV was declared a priority pathogen by the World Health Organization. However, for the treatment of this infection, there is no effective therapy or approved FDA medicines. RNA-dependent polymerase RNA (RdRp) plays an important role in viral replication among the nine well-known proteins of NiV.Material and Methods: Fourteen antiviral molecules have been computerized for NiV RNA-dependent RNA polymerase and demonstrated a potential inhibition effect against coronavirus (NiV-RdRp). A multi-step molecular docking process, followed by extensive analyzes of molecular binding interactions, binding energy estimates, synthetic accessibility assessments, and toxicity tests.Results: Molecular docking analysis reveals that Uprifosbuvir is the most suitable inhibitor for RdRp of Nipah Virus regarding the binding affinity and binding in the target cavity. Although, such studies need clinical confirmation.Conclusion: The role of anti-viral molecules as a ligand against RNA-dependent RNA polymerase is critical important in the current era. Computational tools such as molecular docking has proven its power in the analysis of molecules interaction. Our analysis reveals the Uprifosbuvir might be a candidate RdRp inhibitor. This study should further investigate the properties of the already identified anti-viral molecules followed by a pharmacological investigation of these in-silico findings in suitable models.

scholarly journals MOLECULAR DOCKING STUDY OF NATURALLY OCCURRING COMPOUNDS AS INHIBITORS OF COVID -19

2021 ◽  
pp. 69-71
Author(s):  
SREEDEVI A ◽  
MALAR RETNA A ◽  
ROBIN KUMAR SAMUEL
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Discovery Studio ◽  
Naturally Occurring ◽  
Short Period ◽  
The Right ◽  
Native Ligand ◽  
Made In

Objectives: The worldwide spread of COVID-19 is an emergent issue to be tackled. Currently, several works in various field have been made in rather short period. The present study aimed to assess bioactive compounds found in medicinal plants as potential COVID-19 Mpro inhibitors using molecular docking study. Methods: The docking analyses were performed by using Autodock, Discovery Studio Visualiser and Igemdock. Results: The binding energy obtained from the docking of 6LU7 with native ligand cupressuflavone is -8.9 kcal/mol. Conclusion: These findings will provide the opportunities to identify the right drug to combat COVID-19.

scholarly journals In silico docking analysis of selective bioactive compounds of Phyllanthus acidusaqueousfruit extractagainst MAPK1

Biomedicine ◽  
2021 ◽  
Vol 41 (2) ◽  
pp. 349-357
Author(s):  
E. Padmini ◽  
M. Kavitha
Keyword(s):  
Binding Energy ◽  
Cell Survival ◽  
Bioactive Compounds ◽  
In Silico ◽  
Docking Study ◽  
Mitogen Activated Protein Kinase ◽  
Molecular Docking Study ◽  
Ligand Complex ◽  
In Silico Docking ◽  
Methyl Prednisolone

Introduction and Aim: Phyllanthus acidus L.Skeels (Family: Phyllanthaceae) or Star Gooseberry which bears small, edible, juicy, sour, yellow berries fruit is known as a “liver tonic” in ayurvedic medicine. However, the behavior of the plant fruit or its constituents in cell apoptosis/cell survival is unknown. Hence, the purpose of thepresent study was to perform an in silico docking of selective bioactive compounds of aqueous extract of fruit of P.acidus (PAFAE) against MAPK1. Mitogen activated protein kinase is a family of serine threonine specific protein kinases- MAPK1/ERK1/2, JNK1-3, p38MAPK and ERK5.Activation ofMAPK1 promotes cell survival in certain tissues by inhibiting proapoptotic proteins and by stimulating anti apoptotic factors.   Methodology: In silico docking studies was carried out using bioinformatics tools.The active compounds (Trihomovitamin D3; 2Z,6Z,8Z,12E Hexadecatetraenoic acid, Methyl prednisolone, Hydroxysalmeterol and Tridesacetoxykhivorin) ofP.acidus aqueous fruit extract were docked against MAPK1 resulting in receptor-ligand complex.   Results: The binding energy is correlated with the probability of affinity and stable bound between ligand and its receptor.   Conclusion: The molecular docking study of selective bioactive compounds of PAFAE with MAPK1 protein revealed that Tridesacetoxykhivorinand Methyl Prednisolone, is having good interaction in favorable pose with MAPK1 as shownfrom theireffective binding energy(-7.79kcal/mol and -7.19 kcal/mol), strong bond length and interactions with active site of MAPK1.

scholarly journals Virtual molecular docking study of some novel carboxamide series as new anti-tubercular agents

2020 ◽  
Vol 11 (1) ◽  
pp. 30-36 ◽  
Author(s):  
Mustapha Abdullahi ◽  
Adamu Uzairu ◽  
Gideon Adamu Shallangwa ◽  
David Ebuka Arthur ◽  
Bello Abdullahi Umar ◽  
...  
Keyword(s):  
Binding Energy ◽  
Active Sites ◽  
Docking Simulation ◽  
Docking Study ◽  
Amino Acid Residues ◽  
Ant System ◽  
Molecular Docking Study ◽  
Molegro Virtual Docker ◽  
Chemical Structures ◽  
Hydrogen Bond Interactions

A virtual docking simulation study was performed on thirty-five newly discovered compounds of N-(2-phenoxy) ethyl imidazo[1,2-a] pyridine-3-carboxamide (IPA), to explore their theoretical binding energy and pose with the active sites of the Mycobacterium tuberculosis target (DNA gyrase). The chemical structures of the compounds were drawn correctly with ChemDraw Ultra software, and then geometrically optimized at DFT level of theory with Spartan 14 software package. Consequently, the docking analysis was carried out using Molegro Virtual Docker (MVD). Five complexes (Complex 5, 24, 25, 33 and 35) with high binding energy were selected to examine their binding pose with the active sites of the protein. The docking results suggested a good MolDock score (≥ -90 kcal/mol) and Protein-Ligand ANT System (PLANTS) score (≥ -60 kcal/mol) which depicted that the compounds can efficiently bind with the active sites of the target. However, compound 5 has the best binding pose with the MolDock score of -140.476 kcal/mol which formed three hydrogen bond interactions with the Gln 538, Ala 531, and Ala 533 amino acid residues. This research gives a firsthand theoretical knowledge to improve the binding efficiency of these compounds with the target.

scholarly journals Exploring the Conformational Dynamics of RNA Dependent RNA Polymerase of SARS-CoV-2 in the Presence of Various Nucleotide Analogues

2020 ◽  
Author(s):  
Shruti Koulgi ◽  
Vinod Jani ◽  
Mallikarjunachari Uppuladinne V N ◽  
Uddhavesh Sonavane ◽  
Rajendra Joshi
Keyword(s):  
Rna Polymerase ◽  
Conformational Dynamics ◽  
Principal Component ◽  
Inhibitory Effect ◽  
New Drugs ◽  
Strong Interactions ◽  
Binding Motif ◽  
Entry Site ◽  
Rna Dependent Rna Polymerase ◽  
Nucleotide Analogues

<p>RNA dependent RNA polymerase (RdRP) from positive stranded RNA viruses has always been a hot target for designing of new drugs as it is responsible for viral replication. The major class of drugs that are targeted against RdRP are nucleotide analogues. An extensive docking and molecular dynamics study describing the role of natural nucleotides (NTPs) and its analogues in imparting an inhibitory effect on the RdRP has been presented here. RdRP simulations in its apo, NTP-bound and analogue-bound form have been performed for a cumulative time of 1.9 μs. The conformational flexibility of the RdRP molecule was explored using Principal Component Analysis (PCA) and Markov State Modeling (MSM) Analysis. PCA inferred the presence of correlated motions along the conserved motifs of the RdRP. The ligand binding motif F and template binding motif G showed motions that are negatively correlated with one another. LYS 551, ARG 553 and ARG 555 which are a part of the motif F appear to form strong interactions with the ligand molecules. ARG 836, a primer binding residue was observed to strongly bind to the nucleotide analogues. The MSM analysis helped to observe different conformational states explored by the RdRP. The ensemble docking of the ligands on the Markov states suggested the involvement of the above residues in ligand interactions. The Markov states obtained clearly demarcated the open and closed conformations. The closed states were observed to have more favorable docking of the ligands. MSM analysis predicted a probable inhibitory mechanism involving the closing of the template entry site by reduction in the distance between the flanking finger and thumb subdomain. </p>

In silico investigation of Alliin as potential activator for AMPA receptor

2021 ◽  
Author(s):  
Hilal Ozturk ◽  
N. Yorulmaz ◽  
Mustafa Durgun ◽  
Harun Basoglu
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Ampa Receptor ◽  
Docking Study ◽  
Binding Energies ◽  
Molecular Docking Study ◽  
Gaba A ◽  
Docking Method ◽  
Ampa And Nmda Receptors ◽  
The Central Nervous System

Abstract Natural products from plants, such as flavonoids, arouse immense interest in medicine because of the therapeutic and many other bioactive properties. The molecular docking is a very useful method to screen the molecules based on their free binding energies and give important structural suggestions about how molecules might activate or inhibit the target receptor by comparing reference molecules. Alliin and Allicin differ from many other flavonoids because of containing no benzene rings and having nitrogen and sulfur atoms in their structure. In this study Alliin and Allicin affinity on AMPA, NMDA and GABA-A receptors were evaluated in the central nervous system by using the molecular docking method. Both Alliin and Allicin indicated no inhibitory effects. However Alliin showed significant selectivity to human AMPA receptor (3RN8) as an excitatory. The binding energy of glutamate to 3RN8 was -6.61 kcal/mol, while the binding energy of Allin was -8.08 kcal/mol. Furthermore Alliin’s affinity to the other AMPA and NMDA receptors is quite satisfactory compared to the reference molecule glutamate. In conclusion based on the molecular docking study, Alliin can be useful for synaptic plasticity studies whereas might be enhance seizure activity because of the increased permeability to cations. It also can be beneficial to improve learning and memory and can be used as a supportive product to the hypofunction of NMDA associated problems.

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