scholarly journals A threefold approach including quantum chemical, molecular docking and molecular dynamic studies to explore the natural compounds from Centaurea jacea as the potential inhibitors for COVID-19

2023 ◽  
Vol 83 ◽  
Author(s):  
S. Muhammad ◽  
M. F. Maqbool ◽  
A. G. Al-Sehemi ◽  
A. Iqbal ◽  
M. Khan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Molecular Dynamic ◽  
Bioactive Compounds ◽  
Quantum Chemical ◽  
Hydrophobic Interactions ◽  
Binding Energies ◽  
Perennial Herb ◽  
Drug Candidate ◽  
Aqueous Environment ◽  
Centaurea Jacea

Abstract In the current report, we studied the possible inhibitors of COVID-19 from bioactive constituents of Centaurea jacea using a threefold approach consisting of quantum chemical, molecular docking and molecular dynamic techniques. Centaurea jacea is a perennial herb often used in folk medicines of dermatological complaints and fever. Moreover, anticancer, antioxidant, antibacterial and antiviral properties of its bioactive compounds are also reported. The Mpro (Main proteases) was docked with different compounds of Centaurea jacea through molecular docking. All the studied compounds including apigenin, axillarin, Centaureidin, Cirsiliol, Eupatorin and Isokaempferide, show suitable binding affinities to the binding site of SARS-CoV-2 main protease with their binding energies -6.7 kcal/mol, -7.4 kcal/mol, -7.0 kcal/mol, -5.8 kcal/mol, -6.2 kcal/mol and -6.8 kcal/mol, respectively. Among all studied compounds, axillarin was found to have maximum inhibitor efficiency followed by Centaureidin, Isokaempferide, Apigenin, Eupatorin and Cirsiliol. Our results suggested that axillarin binds with the most crucial catalytic residues CYS145 and HIS41 of the Mpro, moreover axillarin shows 5 hydrogen bond interactions and 5 hydrophobic interactions with various residues of Mpro. Furthermore, the molecular dynamic calculations over 60 ns (6×106 femtosecond) time scale also shown significant insights into the binding effects of axillarin with Mpro of SARS-CoV-2 by imitating protein like aqueous environment. From molecular dynamic calculations, the RMSD and RMSF computations indicate the stability and dynamics of the best docked complex in aqueous environment. The ADME properties and toxicity prediction analysis of axillarin also recommended it as safe drug candidate. Further, in vivo and in vitro investigations are essential to ensure the anti SARS-CoV-2 activity of all bioactive compounds particularly axillarin to encourage preventive use of Centaurea jacea against COVID-19 infections.

scholarly journals Discovery of Fungal Metabolites Bergenin, Quercitrin and Dihydroartemisinin as Potential Inhibitors Against Main Protease of SARS-CoV-2

2020 ◽  
Author(s):  
Ravi Patel ◽  
Akash Vanzara ◽  
Nimisha Patel ◽  
Ajit Vasava ◽  
Sachin Patil ◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Active Site ◽  
Electrostatic Interactions ◽  
Hydrophobic Interactions ◽  
Binding Energies ◽  
Crystallographic Structure ◽  
Medicinal Uses ◽  
Main Protease ◽  
Cyathus Stercoreus ◽  
Potential Inhibitors

Emergence of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection has given rise to COVID-19 pandemic, that is wreaking havoc worldwide. Therefore, there is an urgent need to find out novel drugs to combat SARS-CoV-2 infection. In this backdrop, the present study was aimed to assess potent bioactive compounds from different fungi as potential inhibitors of SARS-CoV-2 main protease (M<sup>pro</sup>) using an <i>in-silico</i> analysis. Nearly 118 bioactive compounds were extracted from <i>Dictyophora indusiata</i>, <i>Geassstrum triplex</i> and <i>Cyathus stercoreus </i>and identified using HR LC/MS analysis. Of which, only bergenin (<i>D. indusiata</i>), quercitrin (<i>G. triplex</i>) and dihydroartemisinin (<i>C. stercoreus</i>) were selected based on their medicinal uses, binding score and active site covered. The 6LU7, a protein crystallographic structure of SARS-CoV-2 M<sup>pro</sup>, was docked with bergenin, quercitrin and dihydroartemisinin using Autodock 4.2 and the binding energies obtained were -7.86, -10.29 and -7.20 kcal/mol, respectively. Bergenin, quercitrin and dihydroartemisinin formed hydrogen bond, electrostatic interactions and hydrophobic interactions with foremost active site amino acids THR190, GLU166, GLN189, GLY143, HIS163, HIS164, CYS145 and PHE140. Present investigation suggests that these three drugs may be used as alternative inhibitors against SARS-CoV-2 M<sup>pro</sup>. However, further research is necessary to assess <i>in vitro</i> potential of these drugs. To the best of our knowledge, present investigation reported these three bioactive compounds of fungal origin for the first time.

Screening of Potent Inhibitors Against 2019 Novel Coronavirus (Covid-19) from Alliumsativum and Allium cepa: An In Silico Approach

2020 ◽  
Vol 11 (1) ◽  
pp. 7981-7993
Keyword(s):  
Molecular Docking ◽  
Allium Cepa ◽  
In Silico ◽  
Treatment Options ◽  
Natural Compounds ◽  
Binding Energies ◽  
Drug Candidate ◽  
Molecular Docking Study ◽  
Standard Drug ◽  
Main Protease

The infection of the global COVID-19 pandemic and the absence of any possible treatment options warrants the use of all available resources to find effective drugs against this scourge. Various ongoing researches have been searching for the new drug candidate against COVID-19 infection. The research objective is based on the molecular docking study of inhibition of the main protease of COVID-19 by natural compounds found in Allium sativum and Allium cepa. Lipinski rule of five and Autodock 4.2 was used by using the Lamarckian Genetic Algorithm to perform Molecular docking to analyze the probability of docking. Further, ADME analysis was also performed by using SwissADME, which is freely available on the web. In the present study, we identified S-Allylcysteine sulfoxide (Alliin), S-Propyl cysteine, S-Allylcysteine, S-Ethylcysteine, S-Allylmercaptocysteine, S-Methylcysteine, S-propyl L-cysteine with binding energies (-5.24, -4.49, -4.99, -4.91, -4.79, -4.76, -5.0 kcal/mol) as potential inhibitor candidates for COVID-19. Out of 7 selected compounds, alliin showed the best binding efficacy with target protein 6LU7. In silico ADME analysis revealed that these compounds are expected to have a standard drug-like property as well. Our findings propose that natural compounds from garlic and onion can be used as potent inhibitors against the main protease of COVID-19, which could be helpful in combating the COVID-19 pandemic.

scholarly journals Structure-Based Virtual Screening and Molecular Dynamic Simulation Studies to Identify Novel Cytochrome bc1 Inhibitors as Antimalarial Agents

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Rahul P. Gangwal ◽  
Gaurao V. Dhoke ◽  
Mangesh V. Damre ◽  
Kanchan Khandelwal ◽  
Abhay T. Sangamwar
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
Molecular Dynamic Simulation ◽  
Molecular Dynamic ◽  
Dynamic Simulation ◽  
Hydrophobic Interactions ◽  
Binding Free Energy ◽  
Van Der Waals Interactions ◽  
Electrostatic Energy ◽  
Hydrogen Bond Acceptor

Cytochrome bc1 (EC 1.10.2.2, bc1) is an essential component of the cellular respiratory chain, which catalyzes electron transfer from quinol to cytochrome c and concomitantly the translocation of protons across the membrane. It has been identified as a promising target in malaria parasites. The structure-based pharmacophore modelling and molecular dynamic simulation approach have been employed to identify novel inhibitors of cytochrome bc1. The best structure-based pharmacophore hypothesis (Hypo1) consists of one hydrogen bond acceptor (HBA), one general hydrophobic (HY), and two hydrophobic aromatic features (HYAr). Further, hydrogen interactions and hydrophobic interactions of known potent inhibitors with cytochrome bc1 were compared with Hypo1, which showed that the Hypo1 has good predictive ability. The validated Hypo1 was used to screen the chemical databases. The hits obtained were subsequently subjected to the molecular docking analysis to identify false-positive hits. Moreover, the molecular docking results were further validated by molecular dynamics simulations. Binding-free energy analysis using MM-GBSA method reveals that the van der Waals interactions and the electrostatic energy provide the basis for favorable absolute free energy of the complex. The five virtual hits were identified as possible candidates for the designing of potent cytochrome bc1 inhibitors.

scholarly journals Computational approach to design of aptamers to the receptor binding domain of SARS-CoV-2

2021 ◽  
pp. 66-67
Author(s):  
P.V. Artyushenko ◽  
◽  
V.A. Mironov ◽  
D.I. Morozov ◽  
I.A. Shchugoreva ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Molecular Dynamic ◽  
Quantum Chemical Calculations ◽  
In Silico ◽  
Quantum Chemical ◽  
Computational Approach ◽  
Receptor Binding Domain ◽  
Dynamic Simulations ◽  
X Ray ◽  
X Ray Scattering

The aim of the research. In this work, in silico selection of DNA-aptamers to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein was performed using molecular modeling methods. Material and methods. A new computational approach to aptamer in silico selection is based on a cycle of simulations, including the stages of molecular modeling, molecular docking, molecular dynamic simulations, and quantum chemical calculations. To verify the obtained calculated results flow cytometry, fluorescence polarization, and small-angle X-ray scattering methods were applied. Results. An initial library consisted of 256 16-mer oligonucleotides was modeled. Based on molecular docking results, the only one aptamer (Apt16) was selected from the library as a starting aptamer to the RBD protein. For Apt16/RBD complex, molecular dynamic and quantum chemical calculations revealed the pairs of nucleotides and amino acids whose contribution to the binding between aptamer and RBD is the largest. Taking into account these data, Apt16 was subjected to the structure modifi cations in order to increase the binding with the RBD. Th us, a new aptamer Apt25 was designed. Th e procedure of 1) aptamer structure modeling/modifi cation, 2) molecular docking, 3) molecular dynamic simulations, 4) quantum chemical calculations was performed several times. As a result, four aptamers (Apt16, Apt25, Apt27, Apt31) to the RBD were designed in silico without any preliminary experimental data. Binding of the each modeled aptamer to the RBD was studied in terms of interactions between residues in protein and nucleotides in the aptamers. Based on the simulation results, the strongest binding with the RBD was predicted for two Apt27 and Apt31aptamers. The calculated results are in good agreement with experimental data obtained by flow cytometry, fluorescence polarization, and small-angle X-ray scattering methods. Conclusion. Th e proposed computational approach to selection and refi nement of aptamers is universal and can be used for wide range of molecular ligands and targets

scholarly journals Molecular Docking Analysis of Chloroquine and Hydroxychloroquine and Design of Anti-SARS-CoV2 Protease Inhibitor

2020 ◽  
Vol 14 (10) ◽  
pp. 52
Author(s):  
Usman Abdulfatai ◽  
Adamu Uzairu ◽  
Gideon Adamu Shallangwa ◽  
Sani Uba
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Binding Energy ◽  
Binding Site ◽  
Docking Simulation ◽  
Binding Energies ◽  
Drug Candidate ◽  
Molecular Docking Study ◽  
Docking Analysis ◽  
Molecular Docking Analysis

In this present investigation, simulated molecular docking study of chloroquine and hydroxychloroquine compounds were investigated on the SARS-CoV2 enzyme to determine the types of amino acids responsible for the biochemical reaction at the binding site. A structure-based docking design technique was explored in designing a novel derivative of chloroquine for the treatment and management of new COVID 19 disease. To achieve this, the molecular docking simulation method was used to investigate the level of chloroquine and hydroxychloroquine (Drugs presently under clinical trial) interactions on SARS-CoV2 enzyme (a causative agent of COVID 19 disease). Chloroquine and hydroxychloroquine which has been debated as drugs for the management of COVID 19 were subjected to molecular docking analysis, and the binding energies generated were found to be -6.1 kcal/mol and -6.8 kcal/mol respectively. Moreover, novel 2-((4-((7-chloroquinolin-4 yl) amino)pentyl)((methylamino)methyl)amino) ethan-1-ol as an anti-SARS-CoV2 protease was designed through the structural modification of hydroxychloroquine. The binding energy of this drug candidate was found to be -6.9 kcal/mol. This novel drug was found to formed hydrogen and conventional interactions with the binding site of SARS-CoV2 protease through amino acids such as Glutamic acid (GLU166), Glycine (GLY143), Phenylalanine (PHE140), Asparagine (ASN142), Histidine (HIS163), His (HIS172, HIS41, HIS163), Leucine (LEU41, LEU27), Glycine (GLY143), Glutamine (GLN189), Methionine (MET49, MET165), Serine (SER 46), Cysteine (CYS145) and Threonine (THR25). With this binding energy, this new drug candidate could bind better to the human SARS-CoV2 protease&rsquo; binding site. This research provides a clue for other scientists on various ways of designing and identify the types of amino acids that may be responsible for biochemical action on SARS-CoV2 protease.

scholarly journals Identification of Dietary Molecules as Therapeutic Agents to Combat COVID-19 Using Molecular Docking Studies

2020 ◽  
Author(s):  
Mohammad Faheem Khan ◽  
Mohsin Ali Khan ◽  
Zaw Ali Khan ◽  
Tanveer Ahamad ◽  
Waseem Ahmad Ansari
Keyword(s):  
Molecular Docking ◽  
Antiviral Agents ◽  
Epigallocatechin Gallate ◽  
World Health Organisation ◽  
Therapeutic Agents ◽  
Binding Energies ◽  
World Health ◽  
Major Constituent ◽  
Drug Candidate ◽  
Health Crisis

Abstract Recently, a new and fatal strain of coronavirus named as SARS-CoV-2 (Disease: COVID-19) appeared in Wuhan, China in December of 2019. Due to its fast growing human to human transmission and confirmed cases in nearly every country, it has been declared as pandemic by World Health Organisation (WHO) on 11 March 2020. Till now, there is no therapy such as vaccines and specific therapeutic agents available globally. Inspite of this, some protease inhibitors and antiviral agents namely lopinavir, ritonavir, remdisivir and chloroquine are under investigation and also implemented in several countries as therapeutic agents for the treatment of COVID-19. Seeing the health crisis across the world, it was our aim to find out a suitable drug candidate which could target SARS-CoV-2. For this purpose, molecular docking of 7 proteinsof SARS-CoV-2 was done with 18active constituents that have previously been reported to be antiviral or anti-SARS-CoV agents. The docking results of these 18 compounds were compared with 2 FDA approved drugs that have are currently being used in COVID 19, namely Remdesivir and Chloroquine. Our result revealed that among all, epigallocatechin gallate (EGCG), a major constituent of green tea, is the lead compound that could fit well into the binding sites of docked proteins of SARS-CoV-2. EGCG showed very strong molecular interactions with binding energies -9.30, -8.66, -8.38, -7.57, -7.26, -6.99 and -4.90 kcal/mole for6y2e, 6vw1, 6vww, 6lxt,6vsb, 6lu7 and 6lvnproteins of SARS-CoV-2, respectively.Therefore, EGCG as per our results, should be explored as a drug candidate for the treatment of COVID-19.

scholarly journals Discovery of Fungal Metabolites Bergenin, Quercitrin and Dihydroartemisinin as Potential Inhibitors Against Main Protease of SARS-CoV-2

2020 ◽  
Author(s):  
Ravi Patel ◽  
Akash Vanzara ◽  
Nimisha Patel ◽  
Ajit Vasava ◽  
Sachin Patil ◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Active Site ◽  
Electrostatic Interactions ◽  
Hydrophobic Interactions ◽  
Binding Energies ◽  
Crystallographic Structure ◽  
Medicinal Uses ◽  
Main Protease ◽  
Cyathus Stercoreus ◽  
Potential Inhibitors

Emergence of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection has given rise to COVID-19 pandemic, that is wreaking havoc worldwide. Therefore, there is an urgent need to find out novel drugs to combat SARS-CoV-2 infection. In this backdrop, the present study was aimed to assess potent bioactive compounds from different fungi as potential inhibitors of SARS-CoV-2 main protease (M<sup>pro</sup>) using an <i>in-silico</i> analysis. Nearly 118 bioactive compounds were extracted from <i>Dictyophora indusiata</i>, <i>Geassstrum triplex</i> and <i>Cyathus stercoreus </i>and identified using HR LC/MS analysis. Of which, only bergenin (<i>D. indusiata</i>), quercitrin (<i>G. triplex</i>) and dihydroartemisinin (<i>C. stercoreus</i>) were selected based on their medicinal uses, binding score and active site covered. The 6LU7, a protein crystallographic structure of SARS-CoV-2 M<sup>pro</sup>, was docked with bergenin, quercitrin and dihydroartemisinin using Autodock 4.2 and the binding energies obtained were -7.86, -10.29 and -7.20 kcal/mol, respectively. Bergenin, quercitrin and dihydroartemisinin formed hydrogen bond, electrostatic interactions and hydrophobic interactions with foremost active site amino acids THR190, GLU166, GLN189, GLY143, HIS163, HIS164, CYS145 and PHE140. Present investigation suggests that these three drugs may be used as alternative inhibitors against SARS-CoV-2 M<sup>pro</sup>. However, further research is necessary to assess <i>in vitro</i> potential of these drugs. To the best of our knowledge, present investigation reported these three bioactive compounds of fungal origin for the first time.

scholarly journals A Computational Study to Identify Potential Inhibitors of SARS-CoV-2 Main Protease (Mpro) from Eucalyptus Active Compounds

Computation ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 79
Author(s):  
Ibrahim Ahmad Muhammad ◽  
Kanikar Muangchoo ◽  
Auwal Muhammad ◽  
Ya’u Sabo Ajingi ◽  
Ibrahim Yahaya Muhammad ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Computational Study ◽  
Md Simulations ◽  
Binding Energies ◽  
Drug Candidate ◽  
Global Public Health ◽  
Main Protease ◽  
Poisson Boltzmann ◽  
Potential Inhibitors

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was found to be a severe threat to global public health in late 2019. Nevertheless, no approved medicines have been found to inhibit the virus effectively. Anti-malarial and antiviral medicines have been reported to target the SARS-CoV-2 virus. This paper chose eight natural eucalyptus compounds to study their binding interactions with the SARS-CoV-2 main protease (Mpro) to assess their potential for becoming herbal drugs for the new SARS-CoV-2 infection virus. In-silico methods such as molecular docking, molecular dynamics (MD) simulations, and Molecular Mechanics Poisson Boltzmann Surface Area (MM/PBSA) analysis were used to examine interactions at the atomistic level. The results of molecular docking indicate that Mpro has good binding energy for all compounds studied. Three docked compounds, α-gurjunene, aromadendrene, and allo-aromadendrene, with highest binding energies of −7.34 kcal/mol (−30.75 kJ/mol), −7.23 kcal/mol (−30.25 kJ/mol), and −7.17 kcal/mol (−29.99 kJ/mol) respectively, were simulated with GROningen MAchine for Chemical Simulations (GROMACS) to measure the molecular interactions between Mpro and inhibitors in detail. Our MD simulation results show that α-gurjunene has the strongest binding energy of −20.37 kcal/mol (−85.21 kJ/mol), followed by aromadendrene with −18.99 kcal/mol (−79.45 kJ/mol), and finally allo-aromadendrene with −17.91 kcal/mol (−74.95 kJ/mol). The findings indicate that eucalyptus may be used to inhibit the Mpro enzyme as a drug candidate. This is the first computational analysis that gives an insight into the potential role of structural flexibility during interactions with eucalyptus compounds. It also sheds light on the structural design of new herbal medicinal products against Mpro.

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