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>

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 Hordatines as a Potential Inhibitor of COVID-19 Main Protease and RNA Polymerase: An In-Silico Approach

2020 ◽  
Author(s):  
Mostafa ◽  
Mohammed ◽  
Hatem
Keyword(s):  
Rna Polymerase ◽  
Drug Targets ◽  
Antiviral Agents ◽  
Docking Studies ◽  
Binding Affinities ◽  
Operating Environment ◽  
Therapeutic Drugs ◽  
Main Protease ◽  
Binding Residues ◽  
Native Ligand

Abstract Total 40 natural compounds were selected to perform the molecular docking studies to screen and identify the potent antiviral agents specifically for Severe Acute Respiratory Syndrome Coronavirus 2 that causes coronavirus disease 2019 (COVID-19). The key targets of COVID-19, protease (PDB ID: 6M0K, 6Y2F and 7BQY) and RNA polymerase (PDB ID: 7bV2) were used to dock our target compounds by Molecular Operating Environment (MOE) version 2014.09. After an extensive screening analysis, 20 compounds exhibit good binding affinities to one or more of the COVID-19 targets. 7 out of 20 compounds were predicted to overcome the activity of the 4 drug targets. The top 7 hits are compounds; Flacourticin (3), Sagerinic acid (16), Hordatine A (23), Hordatine B (24), N-feruloyl tyramine dimer (25), Bisavenanthramides B-5 (29) and Vulnibactins (40). According to our results, all these top hits was found to have a better binding scores than Remdesivir, the native ligand in RNA polymerase target (PDB ID: 7bV2). Hordatines are phenolic compounds present in barley, were found to exhibit the highest binding affinity to both protease and polymerase through forming strong hydrogen bonds with the catalytic residues, as well as significant interactions with other receptor-binding residues. These results probably provided an excellent lead candidate for the development of therapeutic drugs against COVID-19. Eventually, animal experiment and accurate clinical trials are needed to confirm the preventive potentials of these compounds.

scholarly journals Hordatines as a Potential Inhibitor of COVID-19 Main Protease and RNA Polymerase: An In-Silico Approach

2020 ◽  
Vol 10 (6) ◽  
pp. 453-462
Author(s):  
Mohammed A. Dahab ◽  
Mostafa M. Hegazy ◽  
Hatem S. Abbass
Keyword(s):  
Rna Polymerase ◽  
Antiviral Agents ◽  
Docking Studies ◽  
Binding Affinities ◽  
Operating Environment ◽  
Score Functions ◽  
Therapeutic Drugs ◽  
Main Protease ◽  
Binding Residues ◽  
Native Ligand

Abstract Total 40 natural compounds were selected to perform the molecular docking studies to screen and identify the potent antiviral agents specifically for Severe Acute Respiratory Syndrome Coronavirus 2 that causes coronavirus disease 2019 (COVID-19). The key targets of COVID-19, protease (PDB ID: 7BQY) and RNA polymerase (PDB ID: 7bV2) were used to dock our target compounds by Molecular Operating Environment (MOE) version 2014.09. We used 3 different conformations of protease target (6M0K, 6Y2F and 7BQY) and two different score functions to strengthen the probability of inhibitors discovery. After an extensive screening analysis, 20 compounds exhibit good binding affinities to one or both COVID-19 targets. 7 out of 20 compounds were predicted to overcome the activity of both targets. The top 7 hits are, flacourticin (3), sagerinic acid (16), hordatine A (23), hordatine B (24), N-feruloyl tyramine dimer (25), bisavenanthramides B-5 (29) and vulnibactins (40). According to our results, all these top hits was found to have a better binding scores than remdesivir, the native ligand in RNA polymerase target (PDB ID: 7bV2). Hordatines are phenolic compounds present in barley, were found to exhibit the highest binding affinity to both protease and polymerase through forming strong hydrogen bonds with the catalytic residues, as well as significant interactions with other receptor-binding residues. These results probably provided an excellent lead candidate for the development of therapeutic drugs against COVID-19. Eventually, animal experiment and accurate clinical trials are needed to confirm the preventive potentials of these compounds. Graphic Abstract

Discovery of Some Antiviral Natural products to fight against Novel Corona Virus (SARS-CoV-2) using Insilico approach

2020 ◽  
Vol 23 ◽  
Author(s):  
Ashish Shah ◽  
Vaishali Patel ◽  
Bhumika Parmar
Keyword(s):  
Binding Affinity ◽  
Protein S ◽  
Docking Studies ◽  
Spike Protein ◽  
Enveloped Viruses ◽  
Bioactivity Prediction ◽  
Corona Virus ◽  
Main Protease ◽  
Antiviral Activities ◽  
Deadly Disease

Background: Novel Corona virus is a type of enveloped viruses with a single stranded RNA enclosing helical nucleocapsid. The envelope consists of spikes on the surface which are made up of proteins through which virus enters into human cells. Until now there is no specific drug or vaccine available to treat COVID-19 infection. In this scenario, reposting of drug or active molecules may provide rapid solution to fight against this deadly disease. Objective: We had selected 30 phytoconstituents from the different plants which are reported for antiviral activities against corona virus (CoVs) and performed insilico screening to find out phytoconstituents which have potency to inhibit specific target of novel corona virus. Methods: We had perform molecular docking studies on three different proteins of novel corona virus namely COVID-19 main protease (3CL pro), papain-like protease (PL pro) and spike protein (S) attached to ACE2 binding domain. The screening of the phytoconstituents on the basis of binding affinity compared to standard drugs. The validations of screened compounds were done using ADMET and bioactivity prediction. Results: We had screened five compounds biscoclaurine, norreticuline, amentoflavone, licoricidin and myricetin using insilico approach. All compounds found safe in insilico toxicity studies. Bioactivity prediction reviles that these all compounds may act through protease or enzyme inhibition. Results of compound biscoclaurine norreticuline were more interesting as this biscoclaurine had higher binding affinity for the target 3CLpro and PLpro targets and norreticuline had higher binding affinity for the target PLpro and Spike protein. Conclusion: Our study concludes that these compounds could be further explored rapidly as it may have potential to fight against COVID-19.

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 Evaluating cepharanthine analogues as natural drugs against SARS-CoV-2

2021 ◽  
Author(s):  
Atsushi Hijikata ◽  
Clara Shionyu-Mitsuyama ◽  
Setsu Nakae ◽  
Masafumi Shionyu ◽  
Motonori Ota ◽  
...  
Keyword(s):  
The Other ◽  
Spike Protein ◽  
Binding Affinities ◽  
Plant Origin ◽  
Docking Simulations ◽  
Main Protease ◽  
Natural Analogues ◽  
Ester Moiety ◽  
A Cell ◽  
Natural Drugs

Cepharanthine is a natural of plant origin, and recently demonstrated to have anti-SARS-CoV-2 activity. In order to evaluate the other natural analogues as a potential COVID-19 drug, a total of 24 compounds resembling cepharanthine were extracted from the KNApSAcK database, and their binding affinities to supposed target proteins, namely, spike protein and main protease of SARS-CoV-2, NPC1, and TPC2, were predicted via molecular docking simulations. Selected analogues were further evaluated by a cell-based SARS-CoV-2 infection assay, and the efficacies of cepharanthine (IC50 1.90 uM) and tetrandrine (IC50 10.37 uM) were demonstrated. From a comparison of the docking conformations of these compounds, the diphenyl ester moiety of the molecules was suggested for a putative pharmacophore of the cepharanthine-analogues.

scholarly journals Harnessing the Sars-cov-2 Spike Protein Binding Affinity to Ace2 Receptor Through Narcotinic Compounds Combined With Adjuvants: an in Silico Insight

2021 ◽  
Author(s):  
Saeedeh Mohammadi ◽  
Esmail Doustkhah ◽  
Nader Sakhaee ◽  
Ayoub Esmailpour ◽  
Mohammad Esmailpour
Keyword(s):  
Binding Affinity ◽  
In Silico ◽  
Muramyl Dipeptide ◽  
Docking Studies ◽  
Spike Protein ◽  
Binding Affinities ◽  
Narcotic Analgesics ◽  
S Protein ◽  
Suitable Combination ◽  
Spike Proteins

Abstract Protein products of SARS-CoV-2 spike (S) coding gene sequence, were all analyzed and compared to other SARS-CoV S proteins to elucidate structural similarities of spike proteins. A homology modeling of SARS-CoV-2 S protein was obtained and used in molecular docking studies to find binding affinities of spike protein for angiotensin-converting enzyme 2 (ACE2). The two most important binding sites of S protein, namely, RBD and CTD, critically responsible for binding interactions, were identified. Finally, binding affinity of RBD and CTD domains of S protein with narcotic analgesics are studied. Moreover, interactions of ACE2 receptor- S protein with narcotic compounds when mixed with small molecule adjuvants to improve the immune response and increase the efficacy of potential vaccines, were taken into consideration. In-silico results suggest that the combination of narcotine hemiacetal with mannide monooleate shows a stronger binding affinity with CTD, while carprofen-muramyl dipeptide and squalene have stronger binding affinities for the RBD portion of S protein. Thus, a suitable combination of these narcotic is proposed to yield potent site-blocking efficacy for ACE2 receptor against SARS-CoV-2 spike proteins.

scholarly journals Current Trends in SPR Biosensing of SARS-CoV-2 Entry Inhibitors

Chemosensors ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 330
Author(s):  
Elba Mauriz ◽  
Laura M. Lechuga
Keyword(s):  
High Throughput Screening ◽  
Antiviral Agents ◽  
Host Cells ◽  
Binding Affinities ◽  
Entry Inhibitors ◽  
Antiviral Compounds ◽  
Current Trends ◽  
Main Protease ◽  
Emerging Risk ◽  
Repurposed Drugs

The emerging risk of viral diseases has triggered the search for preventive and therapeutic agents. Since the beginning of the COVID-19 pandemic, greater efforts have been devoted to investigating virus entry mechanisms into host cells. The feasibility of plasmonic sensing technologies for screening interactions of small molecules in real time, while providing the pharmacokinetic drug profiling of potential antiviral compounds, offers an advantageous approach over other biophysical methods. This review summarizes recent advancements in the drug discovery process of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) inhibitors using Surface Plasmon Resonance (SPR) biosensors. A variety of SPR assay formats are discussed according to the binding kinetics and drug efficacies of both natural products and repurposed drugs. Special attention has been given to the targeting of antiviral agents that block the receptor binding domain of the spike protein (RBD-S) and the main protease (3CLpro) of SARS-CoV-2. The functionality of plasmonic biosensors for high-throughput screening of entry virus inhibitors was also reviewed taking into account experimental parameters (binding affinities, selectivity, stability), potential limitations and future applications.

scholarly journals Drug Repurposing for Coronavirus (COVID-19): In Silico Screening of Known Drugs Against the SARS-CoV-2 Spike Protein Bound to Angiotensin Converting Enzyme 2 (ACE2) (6M0J)

2020 ◽  
Author(s):  
Konstantinos Kalamatianos
Keyword(s):  
Clinical Trials ◽  
Angiotensin Converting Enzyme ◽  
Experimental Validation ◽  
Antiviral Agents ◽  
Spike Protein ◽  
Binding Affinities ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Lead Compounds ◽  
Virtual Screening Approach

E2/21-12-2020<br><br>In this study FDA approved HCV antiviral drugs and their structural analogues – several of them in clinical trials - were tested for their inhibitory properties towards the SARS-CoV-2 Spike protein bound to angiotensin converting enzyme 2 (ACE2) (6M0J) using a virtual screening approach and computational chemistry methods. The most stable structures and the correspond-ing binding affinities of thirteen such antiretroviral com-pounds were obtained. Frontier molecular orbital theory, global reactivity descriptors, molecular docking calculations and electrostatic potential (ESP) analysis were used to hypothesize the bioactivity of these drugs against 6M0J. It is found that increased affinity for the protein is shown by inhibitors with large compound volume, relatively higher electrophilicity index, aromatic rings and heteroatoms that participate in hydrogen bonding. Amongst the drugs tested, four compounds 10-13 showed excellent results – binding affinities -11.2 to -11.5 kcal.mol-1. These four top scoring compounds may act as lead compounds for further experimental validation, clinical trials and even for the development of more potent antiviral agents against the SARS-CoV-2. <br><br><div><br></div><div>E1/24-08-2020</div><br>In this study FDA approved antiviral drugs and lopinavir analogues in clinical trials were tested for their inhibitory properties towards the SARS-CoV-2 Spike protein bound to<br>angiotensin converting enzyme 2 (ACE2) (6M0J) using a virtual screening approach and computational chemistry methods. Amongst the drugs tested, four compounds, PubChem CID 492005, CID 486507, CID 3010249 and<br><div>lopinavir showed excellent results – binding interactions -9.0 to -9.3 kcal.mol-1. These four top scoring compounds may act as lead compounds for further experimental validation, clinical trials and even for the development of more potent antiviral agents against the SARS-CoV-2.<br> </div><div><br></div>

scholarly journals SARS-CoV-2 Omicron Variant: ACE2 Binding, Cryo-EM Structure of Spike Protein-ACE2 Complex and Antibody Evasion

2021 ◽  
Author(s):  
Dhiraj Mannar ◽  
James W. Saville ◽  
Xing Zhu ◽  
Shanti S. Srivastava ◽  
Alison M. Berezuk ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Hydrogen Bonds ◽  
Binding Affinity ◽  
Spike Protein ◽  
Strong Interactions ◽  
Binding Affinities ◽  
Salt Bridges ◽  
The World

The newly reported Omicron variant is poised to replace Delta as the most rapidly spread SARS-CoV-2 variant across the world. Cryo-EM structural analysis of the Omicron variant spike protein in complex with human ACE2 reveals new salt bridges and hydrogen bonds formed by mutated residues R493, S496 and R498 in the RBD with ACE2. These interactions appear to compensate for other Omicron mutations such as K417N known to reduce ACE2 binding affinity, explaining our finding of similar biochemical ACE2 binding affinities for Delta and Omicron variants. Neutralization assays show that pseudoviruses displaying the Omicron spike protein exhibit increased antibody evasion, with greater evasion observed in sera obtained from unvaccinated convalescent patients as compared to doubly vaccinated individuals (8- vs 3-fold). The retention of strong interactions at the ACE2 interface and the increase in antibody evasion are molecular factors that likely contribute to the increased transmissibility of the Omicron variant.

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