scholarly journals Marine Brominated Tyrosine Alkaloids as Promising Inhibitors of SARS-CoV-2

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6171
Author(s):  
Amr El-Demerdash ◽  
Afnan Hassan ◽  
Tarek Mohamed Abd Abd El-Aziz ◽  
James D. Stockand ◽  
Reem K. Arafa
Keyword(s):  
Molecular Dynamics ◽  
Vaccine Hesitancy ◽  
Membrane Glycoprotein ◽  
Binding Affinities ◽  
Structural Protein ◽  
Spike Glycoprotein ◽  
Marine Alkaloids ◽  
Main Protease ◽  
The World ◽  
Protein Pockets

There have been more than 150 million confirmed cases of SARS-CoV-2 since the beginning of the pandemic in 2019. By June 2021, the mortality from such infections approached 3.9 million people. Despite the availability of a number of vaccines which provide protection against this virus, the evolution of new viral variants, inconsistent availability of the vaccine around the world, and vaccine hesitancy, in some countries, makes it unreasonable to rely on mass vaccination alone to combat this pandemic. Consequently, much effort is directed to identifying potential antiviral treatments. Marine brominated tyrosine alkaloids are recognized to have antiviral potential. We test here the antiviral capacity of fourteen marine brominated tyrosine alkaloids against five different target proteins from SARS-CoV-2, including main protease (Mpro) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and non-structural protein 10 (nsp10) (PDB ID: 6W4H). These marine alkaloids, particularly the hexabrominated compound, fistularin-3, shows promising docking interactions with predicted binding affinities (S-score = −7.78, −7.65, −6.39, −6.28, −8.84 Kcal/mol) for the main protease (Mpro) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and non-structural protein 10 (nsp10) (PDB ID: 6W4H), respectively, where it forms better interactions with the protein pockets than the native interaction. It also shows promising molecular dynamics, pharmacokinetics, and toxicity profiles. As such, further exploration of the antiviral properties of fistularin-3 against SARS-CoV-2 is merited.

scholarly journals A Computational and Literature-Based Evaluation for a Combination of Chiral Anti-CoV Drugs to Block and Eliminate SARS-CoV-2 Safely

2021 ◽  
Author(s):  
Mohd. Suhail
Keyword(s):  
Side Effects ◽  
Jc Virus ◽  
Computational Study ◽  
Human Cells ◽  
The Body ◽  
Binding Affinities ◽  
Chiral Drugs ◽  
Main Protease ◽  
The World ◽  
Second Wave

<p><a>It has been a great challenge for scientists to develop an anti-covid drug/vaccine with fewer side effects, since the coronavirus began. Of course, the prescription of chiral drugs (chloroquine or hydroxychloroquine) has been proved wrong because these chiral drugs neither kill the virus nor eliminate it from the body, but block SARS-CoV-2 from binding to human cells. Another hurdle in front of the world, is not only the positive test of the patient recovered from coronavirus but also the second wave of Covid 19. Hence, the word demands such a drug or drug combination which not only prevents the entry of SARS-CoV-2 in the human cell but also eliminates it or its material from the body completely. The presented computational study explains (i) why the prescription of chiral drugs was not satisfactory (ii) what types of modification can make their prescription satisfactory (iii) the mechanism of action of chiral drugs (chloroquine and hydroxychloroquine) to block SARS-CoV-2 from binding to human cells, and (iv) the strength of mefloquine to eliminate SARS-CoV-2. As the main protease (M<b><sup>pro</sup></b>) of microbes is considered as an effective target for drug design and development, the binding affinities of mefloquine with the main proteases (M<sup>pros</sup>) of JC virus and SARS-CoV-2, were calculated, and then compared to know the eliminating strength of mefloquine against SARS-CoV-2. The main protease (M<sup>pro</sup>) of JC virus was taken because mefloquine has already shown a tremendous result of eliminating it from the body. The current study includes the docking results and literature data in support of the prescription of a combination of S-(+)-hydroxychloroquine and (+) mefloquine. Besides, the presented study also confirms that the prescription of only hydroxychloroquine would not be so effective as in combined form with mefloquine.</a></p>

scholarly journals A Computational and Literature-Based Evaluation for a Combination of Chiral Anti-CoV Drugs to Block and Eliminate SARS-CoV-2 Safely

2021 ◽  
Author(s):  
Mohd. Suhail
Keyword(s):  
Side Effects ◽  
Jc Virus ◽  
Computational Study ◽  
Human Cells ◽  
The Body ◽  
Binding Affinities ◽  
Chiral Drugs ◽  
Main Protease ◽  
The World ◽  
Second Wave

<p><a>It has been a great challenge for scientists to develop an anti-covid drug/vaccine with fewer side effects, since the coronavirus began. Of course, the prescription of chiral drugs (chloroquine or hydroxychloroquine) has been proved wrong because these chiral drugs neither kill the virus nor eliminate it from the body, but block SARS-CoV-2 from binding to human cells. Another hurdle in front of the world, is not only the positive test of the patient recovered from coronavirus but also the second wave of Covid 19. Hence, the word demands such a drug or drug combination which not only prevents the entry of SARS-CoV-2 in the human cell but also eliminates it or its material from the body completely. The presented computational study explains (i) why the prescription of chiral drugs was not satisfactory (ii) what types of modification can make their prescription satisfactory (iii) the mechanism of action of chiral drugs (chloroquine and hydroxychloroquine) to block SARS-CoV-2 from binding to human cells, and (iv) the strength of mefloquine to eliminate SARS-CoV-2. As the main protease (M<b><sup>pro</sup></b>) of microbes is considered as an effective target for drug design and development, the binding affinities of mefloquine with the main proteases (M<sup>pros</sup>) of JC virus and SARS-CoV-2, were calculated, and then compared to know the eliminating strength of mefloquine against SARS-CoV-2. The main protease (M<sup>pro</sup>) of JC virus was taken because mefloquine has already shown a tremendous result of eliminating it from the body. The current study includes the docking results and literature data in support of the prescription of a combination of S-(+)-hydroxychloroquine and (+) mefloquine. Besides, the presented study also confirms that the prescription of only hydroxychloroquine would not be so effective as in combined form with mefloquine.</a></p>

scholarly journals Evaluation of Phytochemicals of Cassia occidentalis L. for their Binding Affinities to SARS-CoV-2 3C-Like Protease: An in Silico Approach

2020 ◽  
pp. 8-14
Author(s):  
Tohmina Afroze Bondhon ◽  
Md. Aynal Haque Rana ◽  
Anamul Hasan ◽  
Rownak Jahan ◽  
Khoshnur Jannat ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
In Silico ◽  
Binding Affinities ◽  
Autodock Vina ◽  
Cassia Occidentalis ◽  
Main Protease ◽  
In Silico Studies ◽  
The World ◽  
Docking Approach

Aims: Corona virus SARS-CoV-2, otherwise known as COVID-19 has created a pandemic resulting in social and financial crisis throughout the world. The virus has no known drugs or vaccines for preventive or therapeutic purposes. The objective of the present study was to screen phytochemicals from Cassia occidentalis L. in virtual screening (in silico) studies to evaluate their potential of binding to the main 3C-like protease of the virus and so stop its replication. Study Design: Molecular docking approach was used for virtual screening studies. Place and Duration of Study: University of Development Alternative between April and July 2020. Methodology: Molecular docking (blind) were done with the help of Autodock Vina. We have used the pdb file (6LU7) of the main protease of SARS-CoV-2 3C-like protease or SARS-CoV-2 3CLpro (monomeric form) to study binding of the phytochemicals. Results: Of the nine phytochemicals studied, the C-glycosidic flavonoids, cassiaoccidentalins A-C demonstrated excellent binding affinities to the protease. The compounds bound to the active site of the protease with binding energy values of -8.2 to-8.4 kcal/mol. Conclusion: The in silico studies suggest that the compounds merit actual COVID-19 inhibitory tests and have potential for anti-COVID-19 use.

scholarly journals Remdesivir Strongly Binds to both RNA-dependent RNA Polymerase and Main Protease of SARS-CoV-2: Evidence from Molecular Simulations

2020 ◽  
Author(s):  
Hoang Linh Nguyen ◽  
Thai Nguyen ◽  
Duc Toan Truong ◽  
Mai Suan Li
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Rna Polymerase ◽  
Binding Affinity ◽  
Recent Experiment ◽  
Umbrella Sampling ◽  
Rna Dependent Rna Polymerase ◽  
Main Protease ◽  
The World ◽  
Binding Mechanisms

The outbreak of a new coronavirus SARS-CoV-2 (severe acute respiratory syndrome–<br>coronavirus 2) has caused a global CoVid-19 (coronavirus disease 2019) pandemic, resulting in millions of infections and thousands of deaths around the world. There is currently no drug or vaccine for CoVid-19, but it has been revealed that some commercially available drugs are promising, at least for treating symptoms. Among them, Remdesivir, which can block the activity of RNA-dependent RNA polymerase (RdRp) in old SARS-CoV and MERS-CoV viruses, has been prescribed to CoVid-19 patients in many countries. A recent experiment showed that Remdesivir binds to SARS-CoV-2 with an inhibition constant of μM, but the exact target has not been reported. In this work, combining molecular docking, steered molecular dynamics and umbrella sampling we examined its binding affinity to two targets including the main protease (Mpro), also known as 3C-like protease, and RdRp. We showed that Remdesivir binds to Mpro slightly weaker than to RdRp and the corresponding inhibition constants, consistent with the experiment, fall to the μM range. The binding mechanisms of<br>Remdesivir to two targets differ in that electrostatic interaction is the main force in stabilizing the RdRp-Remdesivir complex, while the van der Waals interaction dominates in the MproRemdesivir case. Our result indicates that Remdesivir can target not only RdRp but also Mpro, which can be invoked to explain why this drug is effective in treating Covid-19. We have identified residues of the target protein that make the most important contribution to binding affinity, and this information is useful for drug development for this disease. <br>

Docking Studies of Usnic Acid and Sodium Usnate on SARS CoV-2 Main Protease and Spike Protein RBD

2020 ◽  
Author(s):  
Roopa Guthappa
Keyword(s):  
Infectious Disease ◽  
Antiviral Agents ◽  
Usnic Acid ◽  
Docking Studies ◽  
Spike Protein ◽  
Binding Affinities ◽  
Herbal Supplements ◽  
Main Protease ◽  
The World ◽  
Mouth Wash

<p><b>SARS CoV-2 a pandemic influenza like infectious disease emerged in December 2019 has spread throughout the world within few months. Scientists are trying their best to find medicine and vaccine. Usnic acid and its derivatives as herbal supplements are widely used as mouth wash, cosmetics, antiviral agents. In this study, usnic acid and its derivative-sodium usnate in comparison with favipiravir are docked with main protease and spike protein RBD </b><b>6M0J of SARS Cov-2. Usnic acid and sodium usnate exhibit better binding affinities for main protease and spike RBD. The data has been compared with favipiravir. Favipiravir, usnic acid, sodium usnate shows binding affinity of -4.25, -8.05 and -8.55 kcal/mol respectively with main protease. While favipiravir, usnic acid and sodium usnate exhibit binding affinities of -4.25, -6.02 and -6.53 kcal/mol with spike RBD respectively. One of the interesting features is that the inhibition constant values of usnic acid is 1.27 µM and sodium usnate is 539.86 nM in comparison to favipiravir (764.13 µM) with main protease. </b></p>

scholarly journals Remdesivir Strongly Binds to both RNA-dependent RNA Polymerase and Main Protease of SARS-CoV-2: Evidence from Molecular Simulations

2020 ◽  
Author(s):  
Hoang Linh Nguyen ◽  
Thai Nguyen ◽  
Duc Toan Truong ◽  
Mai Suan Li
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Rna Polymerase ◽  
Binding Affinity ◽  
Recent Experiment ◽  
Umbrella Sampling ◽  
Rna Dependent Rna Polymerase ◽  
Main Protease ◽  
The World ◽  
Binding Mechanisms

The outbreak of a new coronavirus SARS-CoV-2 (severe acute respiratory syndrome–<br>coronavirus 2) has caused a global CoVid-19 (coronavirus disease 2019) pandemic, resulting in millions of infections and thousands of deaths around the world. There is currently no drug or vaccine for CoVid-19, but it has been revealed that some commercially available drugs are promising, at least for treating symptoms. Among them, Remdesivir, which can block the activity of RNA-dependent RNA polymerase (RdRp) in old SARS-CoV and MERS-CoV viruses, has been prescribed to CoVid-19 patients in many countries. A recent experiment showed that Remdesivir binds to SARS-CoV-2 with an inhibition constant of μM, but the exact target has not been reported. In this work, combining molecular docking, steered molecular dynamics and umbrella sampling we examined its binding affinity to two targets including the main protease (Mpro), also known as 3C-like protease, and RdRp. We showed that Remdesivir binds to Mpro slightly weaker than to RdRp and the corresponding inhibition constants, consistent with the experiment, fall to the μM range. The binding mechanisms of<br>Remdesivir to two targets differ in that electrostatic interaction is the main force in stabilizing the RdRp-Remdesivir complex, while the van der Waals interaction dominates in the MproRemdesivir case. Our result indicates that Remdesivir can target not only RdRp but also Mpro, which can be invoked to explain why this drug is effective in treating Covid-19. We have identified residues of the target protein that make the most important contribution to binding affinity, and this information is useful for drug development for this disease. <br>

scholarly journals Virtual Screening of Potential Drug Molecules Against Covid-19 Targets: A Drug Repurposing Approach

2021 ◽  
Vol 11 (1) ◽  
pp. 2965-2980
Keyword(s):  
Virtual Screening ◽  
Drug Repurposing ◽  
Structural Protein ◽  
Drug Molecules ◽  
Main Protease ◽  
The World ◽  
Nelfinavir Mesylate ◽  
Tenofovir Alafenamide ◽  
Approved Drugs ◽  
Fda Approved Drugs

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shattered normal life across the world. This deadly virus displays many variants and has claimed many lives in various countries. Spike protein plays a major role in the transmission and infectivity of this virus. The scientific community is trying hard to reign this virus and save human lives. In this effort, drug repurposing has emerged as a reliable tool to screen FDA-approved drugs. In the present study, we did a virtual screening of 265 FDA-approved drugs against two important covid-19 targets (Non-structural protein & main protease) with PDB IDs 6W4H, 6LU7, and 6W63. A comparative analysis of the best drugs based on docking score, binding energy, and effective hits was done against both targets. Out of 265 molecules, the best 7 molecules showed reliable hits against both targets. Best seven drugs namely Saquinavir, Indinavir, Tenofovir Alafenamide, Ritonavir, Nelfinavir mesylate, Cefiderocol and Plazomicin. Our results suggest that these ligands, in combination or individually, can be taken as novel prospects for developing a drug against SARS CoV-2.

scholarly journals Target SARS-CoV-2: Computation of Binding energies with drugs of Dexamethasone/Umifenovir by Molecular Dynamics using OPLS-AA force field

2020 ◽  
Author(s):  
Sk. Md Na ◽  
M. Srinivasa R
Keyword(s):  
Molecular Dynamics ◽  
Force Field ◽  
Binding Energies ◽  
Drug Binding ◽  
Dynamics Simulation ◽  
Strong Interactions ◽  
Radius Of Gyration ◽  
Binding Affinities ◽  
Mean Square ◽  
Main Protease

Abstract Molecular Dynamics simulation using Gromacs with OPLS-AA force field is performed for 100ns between SARS-CoV-2 main protease and Dexamethasone / Umifenovir drugs at 300 K/1 atm pressure. The trajectory of Root Mean Square Deviation (RMSD) and Radius of Gyration(Rg) emphasized the achievement of equilibrium and compactness. The drug-binding affinities on SARS-CoV-2 main protease are estimated via MM/PBSA method. The sign with magnitude of computed Gibbs free energy indicated the presence of strong interactions between SARS-CoV-2 and drugs of Dexamethasone / Umifenovir. The study revealed that the drug Dexamethasone is more effective over Umifenovir in binding SARS-CoV-2 main protease.

scholarly journals Docking Studies of Usnic Acid and Sodium Usnate on SARS CoV-2 Main Protease and Spike Protein RBD

2020 ◽  
Author(s):  
Roopa Guthappa
Keyword(s):  
Infectious Disease ◽  
Antiviral Agents ◽  
Usnic Acid ◽  
Docking Studies ◽  
Spike Protein ◽  
Binding Affinities ◽  
Herbal Supplements ◽  
Main Protease ◽  
The World ◽  
Mouth Wash

<p><b>SARS CoV-2 a pandemic influenza like infectious disease emerged in December 2019 has spread throughout the world within few months. Scientists are trying their best to find medicine and vaccine. Usnic acid and its derivatives as herbal supplements are widely used as mouth wash, cosmetics, antiviral agents. In this study, usnic acid and its derivative-sodium usnate in comparison with favipiravir are docked with main protease and spike protein RBD </b><b>6M0J of SARS Cov-2. Usnic acid and sodium usnate exhibit better binding affinities for main protease and spike RBD. The data has been compared with favipiravir. Favipiravir, usnic acid, sodium usnate shows binding affinity of -4.25, -8.05 and -8.55 kcal/mol respectively with main protease. While favipiravir, usnic acid and sodium usnate exhibit binding affinities of -4.25, -6.02 and -6.53 kcal/mol with spike RBD respectively. One of the interesting features is that the inhibition constant values of usnic acid is 1.27 µM and sodium usnate is 539.86 nM in comparison to favipiravir (764.13 µM) with main protease. </b></p>

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