ASSESSMENT OF SOME NATURAL BIOACTIVE COMPOUNDS FOR INHIBITORY ACTIVITY AGAINST NOVEL COVID-19: A COMPUTATIONAL STUDY

Terpenoids are major components present in herbal formulations of Ginkgo biloba which are considered to slow down progression of Alzheimer disease. Ginkgolide A, Ginkgolide B, Ginkgolide C, Ginkgolide M, Ginkgolide J, Ginkgolide K and Bilobalide are some of the terpenoids selected for computational theoretical calculations using DFT theory at B3LYP/6-311+G*(d,p) basic set level using Gaussian 16W. To study the interaction between selected terpenoids and selected proteins, molecular docking analysis is carried out using Argus Lab (4.0.1) and Auto Dock (4.2). Calculations are carried out on efficient shape-based search algorithm principle and a score base function to calculate the binding energies between them. ADMET analysis provide properties insight of terpenoids compounds. Results from calculated data reveal that there are possible interactions. This data can help in development of potent protein kinase inhibitor for the treatment of Alzheimer.

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

10.26434/chemrxiv.12523136 ◽

2020 ◽

Cited By ~ 1

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 (Mpro) using an in-silico analysis. Nearly 118 bioactive compounds were extracted from Dictyophora indusiata, Geassstrum triplex and Cyathus stercoreus and identified using HR LC/MS analysis. Of which, only bergenin (D. indusiata), quercitrin (G. triplex) and dihydroartemisinin (C. stercoreus) were selected based on their medicinal uses, binding score and active site covered. The 6LU7, a protein crystallographic structure of SARS-CoV-2 Mpro, 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 Mpro. However, further research is necessary to assess in vitro potential of these drugs. To the best of our knowledge, present investigation reported these three bioactive compounds of fungal origin for the first time.

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

10.26434/chemrxiv.12523136.v1 ◽

2020 ◽

Cited By ~ 1

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 (Mpro) using an in-silico analysis. Nearly 118 bioactive compounds were extracted from Dictyophora indusiata, Geassstrum triplex and Cyathus stercoreus and identified using HR LC/MS analysis. Of which, only bergenin (D. indusiata), quercitrin (G. triplex) and dihydroartemisinin (C. stercoreus) were selected based on their medicinal uses, binding score and active site covered. The 6LU7, a protein crystallographic structure of SARS-CoV-2 Mpro, 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 Mpro. However, further research is necessary to assess in vitro potential of these drugs. To the best of our knowledge, present investigation reported these three bioactive compounds of fungal origin for the first time.

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

Computation ◽

10.3390/computation8030079 ◽

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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Structural Elucidation of SARS-CoV-2 Vital Proteins: Computational Methods Reveal Potential Drug Candidates Against Main Protease, Nsp12 RNA-dependent RNA Polymerase and Nsp13 Helicase

10.20944/preprints202003.0085.v1 ◽

2020 ◽

Cited By ~ 5

Author(s):

Muhammad Usman Mirza ◽

Matheus Froeyen

Keyword(s):

Drug Discovery ◽

Rna Polymerase ◽

High Throughput Screening ◽

Structural Information ◽

Computational Study ◽

Antiviral Drug ◽

Decomposition Analysis ◽

Energy Decomposition Analysis ◽

Rna Dependent Rna Polymerase ◽

Main Protease

The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a major outbreak of coronavirus disease 2019 (COVID-19) and instigated a widespread fear and has threatened global health security. Although phenomenal efforts are in progress to effectively combat this COVID-19 outbreak. Still, no licensed antiviral drugs or vaccines are available, and treatment is limited to supportive care and few repurposed drugs. In this urgency situation, computational drug discovery methods provide both an alternative and a supplement to tiresome high-throughput screening, particularly in the hit-to-lead-optimization stage. Identification of small molecules that specifically target viral replication apparatus has shown the most successful strategy in antiviral drug discovery. The present study deals with the identification of potential compounds that specifically interact with SARS-CoV-2 vital proteins, including main protease (Mpro), Nsp12 RNA-dependent-RNA-polymerase (RdRp) and Nsp13 helicase. A constructive and integrated virtual screening efforts together with molecular dynamics simulations identified potential binding modes and favourable molecular interaction profile of corresponding compounds. Moreover, structurally important binding site residues in conserved motifs located inside the active site are elucidated, which displayed relative importance in ligand binding based on residual energy decomposition analysis. Although the current study lacks experimental validation, the structural information obtained from this computational study paved the way to identify and design specific targeted inhibitors to combat COVID-19 outbreak.

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In Silico Molecular Docking and Molecular Dynamic Simulation of Potential Inhibitors of 3C-like Main Proteinase (3CLpro) from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Using Selected African Medicinal Plants

10.26434/chemrxiv.12480434.v1 ◽

2020 ◽

Author(s):

Sahar Qazi ◽

Mustafa Alhaji Isa ◽

Adam Mustapha ◽

Khalid Raza ◽

Ibrahim Alkali Allamin ◽

...

Keyword(s):

Molecular Docking ◽

Severe Acute Respiratory Syndrome ◽

In Silico ◽

Md Simulation ◽

Binding Energies ◽

Anacardium Occidentale ◽

Upper Respiratory Tract ◽

Ligand Complex ◽

In Silico Docking ◽

Main Protease

The Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) is an infectious virus that causes mild to severe life-threatening upper respiratory tract infection. The virus emerged in Wuhan, China in 2019, and later spread across the globe. Its genome has been completely sequenced and based on the genomic information, the virus possessed 3C-Like Main Protease (3CLpro), an essential multifunctional enzyme that plays a vital role in the replication and transcription of the virus by cleaving polyprotein at eleven various sites to produce different non-structural proteins. This makes the protein an important target for drug design and discovery. Herein, we analyzed the interaction between the 3CLpro and potential inhibitory compounds identified from the extracts of Zingiber offinale and Anacardium occidentale using in silico docking and Molecular Dynamics (MD) Simulation. The crystal structure of SARS-CoV-2 main protease in complex with 02J (5-Methylisoxazole-3-carboxylic acid) and PEJ (composite ligand) (PDB Code: 6LU7,2.16Å) retrieved from Protein Data Bank (PDB) and subject to structure optimization and energy minimization. A total of twenty-nine compounds were obtained from the extracts of Zingiber offinale and the leaves of Anacardium occidentale. These compounds were screened for physicochemical (Lipinski rule of five, Veber rule, and Egan filter), Pan-Assay Interference Structure (PAINS), and pharmacokinetic properties to determine the Pharmaceutical Active Ingredients (PAIs). Of the 29 compounds, only nineteen (19) possessed drug-likeness properties with efficient oral bioavailability and less toxicity. These compounds subjected to molecular docking analysis to determine their binding energies with the 3CLpro. The result of the analysis indicated that the free binding energies of the compounds ranged between ˗5.08 and -10.24kcal/mol, better than the binding energies of 02j (-4.10kcal/mol) and PJE (-5.07kcal.mol). Six compounds (CID_99615 = -10.24kcal/mol, CID_3981360 = 9.75kcal/mol, CID_9910474 = -9.14kcal/mol, CID_11697907 = -9.10kcal/mol, CID_10503282 = -9.09kcal/mol and CID_620012 = -8.53kcal/mol) with good binding energies further selected and subjected to MD Simulation to determine the stability of the protein-ligand complex. The results of the analysis indicated that all the ligands form stable complexes with the protein, although, CID_9910474 and CID_10503282 had a better stability when compared to other selected phytochemicals (CID_99615, CID_3981360, CID_620012, and CID_11697907).

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In Silico Molecular Docking and Molecular Dynamic Simulation of Potential Inhibitors of 3C-like Main Proteinase (3CLpro) from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Using Selected African Medicinal Plants

10.26434/chemrxiv.12480434 ◽

2020 ◽

Author(s):

Sahar Qazi ◽

Mustafa Alhaji Isa ◽

Adam Mustapha ◽

Khalid Raza ◽

Ibrahim Alkali Allamin ◽

...

Keyword(s):

Molecular Docking ◽

Severe Acute Respiratory Syndrome ◽

In Silico ◽

Md Simulation ◽

Binding Energies ◽

Anacardium Occidentale ◽

Upper Respiratory Tract ◽

Ligand Complex ◽

In Silico Docking ◽

Main Protease

The Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) is an infectious virus that causes mild to severe life-threatening upper respiratory tract infection. The virus emerged in Wuhan, China in 2019, and later spread across the globe. Its genome has been completely sequenced and based on the genomic information, the virus possessed 3C-Like Main Protease (3CLpro), an essential multifunctional enzyme that plays a vital role in the replication and transcription of the virus by cleaving polyprotein at eleven various sites to produce different non-structural proteins. This makes the protein an important target for drug design and discovery. Herein, we analyzed the interaction between the 3CLpro and potential inhibitory compounds identified from the extracts of Zingiber offinale and Anacardium occidentale using in silico docking and Molecular Dynamics (MD) Simulation. The crystal structure of SARS-CoV-2 main protease in complex with 02J (5-Methylisoxazole-3-carboxylic acid) and PEJ (composite ligand) (PDB Code: 6LU7,2.16Å) retrieved from Protein Data Bank (PDB) and subject to structure optimization and energy minimization. A total of twenty-nine compounds were obtained from the extracts of Zingiber offinale and the leaves of Anacardium occidentale. These compounds were screened for physicochemical (Lipinski rule of five, Veber rule, and Egan filter), Pan-Assay Interference Structure (PAINS), and pharmacokinetic properties to determine the Pharmaceutical Active Ingredients (PAIs). Of the 29 compounds, only nineteen (19) possessed drug-likeness properties with efficient oral bioavailability and less toxicity. These compounds subjected to molecular docking analysis to determine their binding energies with the 3CLpro. The result of the analysis indicated that the free binding energies of the compounds ranged between ˗5.08 and -10.24kcal/mol, better than the binding energies of 02j (-4.10kcal/mol) and PJE (-5.07kcal.mol). Six compounds (CID_99615 = -10.24kcal/mol, CID_3981360 = 9.75kcal/mol, CID_9910474 = -9.14kcal/mol, CID_11697907 = -9.10kcal/mol, CID_10503282 = -9.09kcal/mol and CID_620012 = -8.53kcal/mol) with good binding energies further selected and subjected to MD Simulation to determine the stability of the protein-ligand complex. The results of the analysis indicated that all the ligands form stable complexes with the protein, although, CID_9910474 and CID_10503282 had a better stability when compared to other selected phytochemicals (CID_99615, CID_3981360, CID_620012, and CID_11697907).

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Nutraceuticals from Marine Bionetworks

Current Nutrition & Food Science ◽

10.2174/1573401314666180109153825 ◽

2019 ◽

Vol 15 (4) ◽

pp. 338-344

Author(s):

Abhitav Tiwari ◽

Shambhawi Pritam ◽

Keerti Mishra ◽

Mehshara Khan ◽

Neeraj Upmanyu ◽

...

Keyword(s):

Dietary Supplements ◽

Bioactive Compounds ◽

Daily Basis ◽

Marine Organisms ◽

Bioactive Molecules ◽

Natural Sources ◽

Nutraceutical Compounds ◽

Potential Sources ◽

Immense Potential ◽

Potential Use

“Nutrition” and “Pharmaceutical” together build up the perception of “Nutraceuticals” that refer to the food or dietary supplements that help to incorporate additional health benefits to the fundamental sustenance accomplished on daily basis. Each nutraceutical contains one or more bioactive molecules that are usually obtained by chemical and/ or biotechnological synthesis or by extraction from natural sources. Among the natural sources, marine bionetwork possess immense potential for the presence of bioactive compounds. Some of these bioactive compounds as isolated from marine sources, have potential use as nutraceuticals. This mini review provides a brief overview of nutraceutical compounds from marine sources that are currently under research and/or have been commercialized. A detailed discussion on the biochemical categories of compounds and the marine organisms that play as potential sources of these bioactive nutraceutical compounds have been included.

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In Silico Docking, ADMET and QSAR Study of few Antimalarial Phytoconstituents as Inhibitors of Plasmepsin II of P. falciparum Against Malaria

Current Drug Therapy ◽

10.2174/1574885514666190923112738 ◽

2020 ◽

Vol 15 (3) ◽

pp. 264-273

Author(s):

Syeda Sabiha Salam ◽

Pankaj Chetia ◽

Devid Kardong

Keyword(s):

Medicinal Plants ◽

In Silico ◽

Computational Study ◽

Binding Energies ◽

Eastern Region ◽

Relationship Analysis ◽

The North ◽

North Eastern ◽

Plasmepsin Ii ◽

Antimalarial Compounds

Background: Malaria is endemic in various parts of India particularly in the North- Eastern states with Plasmodium falciparum-the most prevalent human malaria parasite. Plantderived compounds have always received tremendous importance in the area of drug discovery and development and scientific study of traditional medicinal plants are of great importance to mankind. Objective: The present work deals with the computational study of some antimalarial compounds obtained from a few medicinal plants used by the tribal inhabitants of the North-Eastern region of India for treating malaria. Methods: In silico methodologies were performed to study the ligand-receptor interactions. Target was identified based on the pharmacophore mapping approach. A total of 18 plant-derived compounds were investigated in order to estimate the binding energies of the compounds with their drug target through molecular docking using Autodock 4.2. ADMET filtering for determining the pharmacokinetic properties of the compounds was done using Mobyle@RPBS server. Subsequent Quantitative-Structure Activity Relationship analysis for bioactivity prediction (IC50) of the compounds was done using Easy QSAR 1.0. Results: The docking result identified Salannin to be the most potent Plasmepsin II inhibitor while the QSAR analysis identified Lupeol to have the least IC50 value. Most of the compounds have passed the ADME/Tox filtration. Conclusion: Salannin and Lupeol were found to be the most potent antimalarial compounds that can act as successful inhibitors against Plasmepsin II of P. falciparum. The compounds Salannin and Lupeol are found in Azadirachta indica and Swertia chirata plants respectively, abundantly available in the North-Eastern region of India and used by many inhabiting tribes for the treatment of malaria and its symptoms.

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Current Strategies for Studying the Natural and Synthetic Bioactive Compounds in Food by Chromatographic Separation Techniques

Processes ◽

10.3390/pr9071100 ◽

2021 ◽

Vol 9 (7) ◽

pp. 1100

Author(s):

Wioletta Parys ◽

Małgorzata Dołowy ◽

Alina Pyka-Pająk

Keyword(s):

Gas Chromatography ◽

Bioactive Compounds ◽

Residue Analysis ◽

Food Products ◽

Vital Role ◽

Bioactive Molecules ◽

Validation Parameters ◽

Layer Chromatography ◽

Natural And Synthetic

The present study summarizes the new strategies including advanced equipment and validation parameters of liquid and gas chromatography methods i.e., thin-layer chromatography (TLC), column liquid chromatography (CLC), and gas chromatography (GC) suitable for the identification and quantitative determination of different natural and synthetic bioactive compounds present in food and food products, which play an important role in human health, within the period of 2019–2021 (January). Full characteristic of some of these procedures with their validation parameters is discussed in this work. The present review confirms the vital role of HPLC methodology in combination with different detection modes i.e., HPLC-UV, HPLC-DAD, HPLC-MS, and HPLC-MS/MS for the determination of natural and synthetic bioactive molecules for different purposes i.e., to characterize the chemical composition of food as well as in the multi-residue analysis of pesticides, NSAIDs, antibiotics, steroids, and others in food and food products.

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