scholarly journals Inhibition of SARS-CoV-2 3CL Mpro by Natural and Synthetic Inhibitors: Potential Implication for Vaccine Production Against COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Anwar Ullah ◽  
Kifayat Ullah
Keyword(s):  
Specific Treatment ◽  
Docking Study ◽  
Effective Vaccine ◽  
Molecular Docking Study ◽  
2S Albumin ◽  
Potential Implication ◽  
Catalytic Function ◽  
The World ◽  
Domain Iii ◽  
Natural And Synthetic

COVID-19 has created a pandemic situation all over the world. It has spread in nearly every continent. Researchers all over the world are trying to produce an effective vaccine against this virus, however; no specific treatment for COVID-19 has been discovered -so far. The current work describes the inhibition study of the SARS-CoV-2 main proteinase or 3CL Mpro by natural and synthetic inhibitors, which include 2S albumin and flocculating protein from Moringa oleifera (M. oleifera) and Suramin. Molecular Docking study was carried out using the programs like AutoDock 4.0, HADDOCK2.4, patchdock, pardock, and firedock. The global binding energy of Suramin, 2S albumin, and flocculating proteins were −41.96, −9.12, and −14.78 kJ/mol, respectively. The docking analysis indicates that all three inhibitors bind at the junction of domains II and III. The catalytic function of 3CL Mpro is dependent on its dimeric form, and the flexibility of domain III is considered important for this dimerization. Our study showed that all three inhibitors reduce this flexibility and restrict their motion. The decrease in flexibility of domain III was further confirmed by analysis coming from Molecular dynamic simulation. The analysis results indicate that the temperature B-factor of the enzyme decreases tremendously when the inhibitors bind to it. This study will further explore the possibility of producing an effective treatment against COVID-19.

scholarly journals Molecular Docking Study of the Potential Relevance of the Natural Compounds Isoflavone and Myricetin to COVID-19

2021 ◽  
Vol 25 (3) ◽  
pp. 271-282
Author(s):  
Didik Priyandoko ◽  
◽  
Wahyu Widowati ◽  
Mawar Subangkit ◽  
Diana Jasaputra ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Severe Acute Respiratory Syndrome ◽  
Active Sites ◽  
Docking Study ◽  
Binding Mode ◽  
Molecular Docking Study ◽  
Wuhan City ◽  
The World ◽  
Novel Coronavirus ◽  
Proteins Interactions

The 2019 novel coronavirus (2019-nCoV) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly from its origin in Wuhan City, Hubei Province, China, to the rest of the world. The efficacy of herbal treatment in the control of contagious disease was demonstrated during the 2003 outbreak of severe acute respiratory syndrome (SARS). Natural compound used for this study were isoflavone and myricetin. Molecular docking was performed to analyze binding mode of the compounds towards 12 proteins related to COVID-19. The prediction shows that isoflavone and myricetin have moderate probability of antiviral activity. All of the docked compounds occupied the active sites of the proteins related to COVID-19. Based on QSAR and molecular docking, interactions were predicted with 10 out of 12 potential COVID-19 proteins for myricetin and with 9 out of 12 proteins interactions for isoflavone. A potential disease alleviating action is suggested for isoflavone and myricetin in the context of COVID-19 infection.

scholarly journals Identification of Compounds from Nigella Sativa as New Potential Inhibitors of 2019 Novel Coronasvirus (Covid-19): Molecular Docking Study.

2020 ◽  
Author(s):  
Salim Bouchentouf ◽  
Noureddine Missoum
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Nigella Sativa ◽  
Specific Treatment ◽  
Docking Study ◽  
Clinical Test ◽  
Molecular Docking Study ◽  
Great Opportunity ◽  
Drug Candidates ◽  
Energy Score

<p>The spread of the global COVID-19 pandemic, the lack of specific treatment and the urgent situation requires use of all resources to remedy this scourge. In the present study, using molecular docking, we identify new probable inhibitors of COVID-19 by molecules from <i>Nigella sativa L</i>, which is highly reputed healing herb in North African societies and both Islamic and Christian traditions. The discovery of the M<sup>pro</sup> protease structure in COVID-19 provides a great opportunity to identify potential drug candidates for treatment. Focusing on the main proteases in CoVs (3CL<sup>pro</sup>/M<sup>pro</sup>) (PDB ID 6LU7 and 2GTB); docking of compounds from <i>Nigella Sativa</i> and drugs under clinical test was performed using Molecular Operating Environment software (MOE). Nigelledine docked into 6LU7 active site gives energy complex about -6.29734373 Kcal/mol which is close to the energy score given by chloroquine (-6.2930522 Kcal/mol) and better than energy score given by hydroxychloroquine (-5.57386112 Kcal/mol) and favipiravir (-4.23310471 kcal/mol). Docking into 2GTB active site showed that α- Hederin gives energy score about-6.50204802 kcal/mol whcih is better energy score given by chloroquine (-6.20844936 kcal/mol), hydroxychloroquine (-5.51465893 kcal/mol)) and favipiravir (-4.12183571kcal/mol). Nigellidine and α- Hederin appeared to have the best potential to act as COVID-19 treatment. Further, researches are necessary to testify medicinal use of identified and to encourage preventive use of <i>Nigella Sativa </i>against coronavirus infection.</p>

scholarly journals Identification of Bioactive Phytoconstituents from the Plant Euphorbia hirta as Potential Inhibitor of SARS-CoV-2: an In-Silico Approach

2021 ◽  
Vol 12 (2) ◽  
pp. 1385-1396
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Biological Activities ◽  
Specific Treatment ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Standard Drug ◽  
Euphorbia Hirta ◽  
Main Protease

Currently, the entire globe is under the deadliest pandemic of Covid-19 caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). At present, no specific treatment is available to combat COVID-19 infection. Euphorbia hirta (Euphorbiaceae) have been reported for a variety of biological activities, including antiviral. The present investigation aimed to identify potential phytoconstituents of the plant E. hirta from the category flavonoids and coumarins against the SARS-CoV-2 using in silico approach. The molecular docking studies were performed using two different targets of SARS-CoV-2, namely Main protease (Mpro; PDB ID: 6M2N) and RNA-dependent RNA polymerase (RdRp; PDB ID: 7BW4). Based on the molecular docking study in comparison with standard drug, four compounds, namely Euphrobianin, Quercetin, 3-o-alpha-rhamnoside, Isoquercitrin, and rutin, were screened against the target Mpro. Three phytoconstituents, euphorbianin, myricetin, and rutin, were screened against the target RdRp. In the in silico toxicity studies of screened phytoconstituents, except myrectin all were predicted safe. Results of euphorbianin and rutin were found more interesting as both compounds had high binding affinity against both targets. Finally, we want to conclude that euphrobianin, quercetin 3-o-alpha-rhamnoside, isoquercitrin, and rutin could be further explored rapidly as they may have the potential to fight against COVID-19.

scholarly journals Identification of Compounds from Nigella Sativa as New Potential Inhibitors of 2019 Novel Coronasvirus (Covid-19): Molecular Docking Study

2020 ◽  
Author(s):  
Salim Bouchentouf ◽  
Noureddine Missoum
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Nigella Sativa ◽  
Specific Treatment ◽  
Docking Study ◽  
Clinical Test ◽  
Molecular Docking Study ◽  
Great Opportunity ◽  
Drug Candidates ◽  
Energy Score

The spread of the global COVID-19 pandemic, the lack of specific treatment and the urgent situation requires use of all resources to remedy this scourge. In the present study, using molecular docking, we identify new probable inhibitors of COVID-19 by molecules from Nigella sativa L, which is highly reputed healing herb in North African societies and both Islamic and Christian traditions. The discovery of the Mpro protease structure in COVID-19 provides a great opportunity to identify potential drug candidates for treatment. Focusing on the main proteases in CoVs (3CLpro/Mpro) (PDB ID 6LU7 and 2GTB); docking of compounds from Nigella Sativa and drugs under clinical test was performed using Molecular Operating Environment software (MOE). Nigelledine docked into 6LU7 active site gives energy complex about -6.29734373 Kcal/mol which is close to the energy score given by chloroquine (-6.2930522 Kcal/mol) and better than energy score given by hydroxychloroquine (-5.57386112 Kcal/mol) and favipiravir (-4.23310471 kcal/mol). Docking into 2GTB active site showed that &alpha;- Hederin gives energy score about-6.50204802 kcal/mol whcih is better energy score given by chloroquine (-6.20844936 kcal/mol), hydroxychloroquine (-5.51465893 kcal/mol)) and favipiravir (-4.12183571kcal/mol). Nigellidine and &alpha;- Hederin appeared to have the best potential to act as COVID-19 treatment. Further, researches are necessary to testify medicinal use of identified and to encourage preventive use of Nigella Sativa against coronavirus infection.

scholarly journals Identification of Compounds from Nigella Sativa as New Potential Inhibitors of 2019 Novel Coronasvirus (Covid-19): Molecular Docking Study.

2020 ◽  
Author(s):  
Salim Bouchentouf ◽  
Noureddine Missoum
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Nigella Sativa ◽  
Specific Treatment ◽  
Docking Study ◽  
Clinical Test ◽  
Molecular Docking Study ◽  
Great Opportunity ◽  
Drug Candidates ◽  
Energy Score

<p>The spread of the global COVID-19 pandemic, the lack of specific treatment and the urgent situation requires use of all resources to remedy this scourge. In the present study, using molecular docking, we identify new probable inhibitors of COVID-19 by molecules from <i>Nigella sativa L</i>, which is highly reputed healing herb in North African societies and both Islamic and Christian traditions. The discovery of the M<sup>pro</sup> protease structure in COVID-19 provides a great opportunity to identify potential drug candidates for treatment. Focusing on the main proteases in CoVs (3CL<sup>pro</sup>/M<sup>pro</sup>) (PDB ID 6LU7 and 2GTB); docking of compounds from <i>Nigella Sativa</i> and drugs under clinical test was performed using Molecular Operating Environment software (MOE). Nigelledine docked into 6LU7 active site gives energy complex about -6.29734373 Kcal/mol which is close to the energy score given by chloroquine (-6.2930522 Kcal/mol) and better than energy score given by hydroxychloroquine (-5.57386112 Kcal/mol) and favipiravir (-4.23310471 kcal/mol). Docking into 2GTB active site showed that α- Hederin gives energy score about-6.50204802 kcal/mol whcih is better energy score given by chloroquine (-6.20844936 kcal/mol), hydroxychloroquine (-5.51465893 kcal/mol)) and favipiravir (-4.12183571kcal/mol). Nigellidine and α- Hederin appeared to have the best potential to act as COVID-19 treatment. Further, researches are necessary to testify medicinal use of identified and to encourage preventive use of <i>Nigella Sativa </i>against coronavirus infection.</p>

EVALUATION OF IN-SILICO ANTICANCER POTENTIAL OF PYRETHROIDS: A COMPARATIVE MOLECULAR DOCKING STUDY

2015 ◽  
Author(s):  
Manik Ghosh ◽  
Kamal Kant ◽  
Anoop Kumar ◽  
Padma Behera ◽  
Naresh Rangra ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Study ◽  
Molecular Docking Study

Myricetin Preferentially Binds to Interfacial Regions in Domains 1 – 3 to Inhibit Cholesterol-Dependent Cytolysins: A Molecular Docking Study

2020 ◽  
Author(s):  
Rafael Espiritu
Keyword(s):  
Molecular Docking ◽  
Structural Changes ◽  
Docking Study ◽  
Listeriolysin O ◽  
Molecular Docking Study ◽  
Docking Analysis ◽  
Streptolysin O ◽  
Molecule Inhibitor ◽  
Human Cd59 ◽  
Anthrolysin O

<p>Cholesterol-dependent cytolysins (CDCs) are proteinaceous toxins secreted as monomers by some Gram-positive and Gram-negative bacteria that contribute to their pathogenicity. These toxins bind to either cholesterol or human CD59, leading to massive structural changes, toxin oligomerization, formation of very large pores, and ultimately cell death, making these proteins promising targets for inhibition. Myricetin, and its related flavonoids, have been previously identified as a candidate small molecule inhibitor of specific CDCs such as listeriolysin O (LLO) and suilysin (SLY), interfering with their oligomerization. In this work, molecular docking was performed to assess the interaction of myricetin with other CDCs whose crystal structures are already known. Results indicated that although myricetin bound to the hitherto identified cavity in domain 4 (D4), much more efficient and stable binding was obtained in sites along the interfacial regions of domains 1 – 3 (D1 – D3). This was common among the tested CDCs, which was primarily due to much more extensive stabilizing intermolecular interactions, as indicated by post-docking analysis. Specifically, myricetin bound to (1) the interface of the three domains in anthrolysin O (ALO), perfringolysin O (PFO), pneumolysin (PLY), SLY, and vaginolysin (VLY), (2) at/near the D1/D3 interface in LLO and streptolysin O (SLO), and (3) along the D2/D3 interface in intermedilysin (ILY). These findings provide theoretical basis on the possibility of using myricetin and its related compounds as a broad-spectrum inhibitor of CDCs to potentially address the diseases associated with these pathogens.</p>

Computational Evidences of Phytochemical Mediated Disruption of PLpro Driven Replication of SARS-CoV-2: A Therapeutic Approach Against COVID-19

2020 ◽  
Vol 21 ◽  
Author(s):  
Acharya Balkrishna ◽  
Rashmi Mittal ◽  
Vedpriya Arya
Keyword(s):  
Molecular Docking ◽  
Md Simulation ◽  
Bond Distance ◽  
Immunological Response ◽  
Docking Study ◽  
Receptor Interaction ◽  
Molecular Docking Study ◽  
Replication Process ◽  
Stable Conformation ◽  
Distance Analysis

Background:: COVID-19 caused by SARS-CoV-2 has been declared as global pandemic by WHO. Comprehensive analysis of this unprecedented outbreak may help to fight against the disease and may play a pivotal role in decreasing the mortality rate linked with it. Papain like protease (PLpro), a multifunctional polyprotein facilitates the replication of SARS-CoV-2 and evades it from the host immunological response by antagonizing cytokines, interferons and may be considered as potential drug target to combat the current pandemic. Methods:: Natural moieties obtained from medicinal plants were analysed for their potency to target PLpro of SARS-CoV-2 by molecular docking study and were compared with synthetic analogs named as remdesivir, chloroquine and favipiravir. The stability of complexes of top hits was analysed by MD Simulation and interaction energy was calculated. Furthermore, average RMSD values were computed and deepsite ligand binding pockets were predicted using Play Molecule. Drug like abilities of these moieties were determined using ADMET and bond distance between the ligand and active site was assessed to predict the strength of interaction. Results:: Nimbocinol (-7.6 Kcal/mol) and sage (-7.3 Kcal/mol) exhibited maximum BA against PLpro SARS-CoV-2 as evident from molecular docking study which was found to be even better than remdesivir (-6.1 Kcal/mol), chloroquine (-5.3 Kcal/mol) and favipiravir (-5.7 Kcal/mol). Both nimbocinol-PLpro and sage-PLpro SARS-CoV-2 complex exhibited stable conformation during MD Simulation of 101ns at 310 K and potential, kinetic and electrostatic interaction energies were computed which was observed to be concordant with results of molecular docking study. RMSD average values were found to be 0.496 ± 0.015 Å and 0.598 ± 0.023 Å for nimbocinol and sage respectively thus revealing that both the deviation and fluctuations during MD Simulation were observed to be least. Deepsite prediction disclosed that both compounds occupied cryptic pockets in receptor and non-bond distance analysis revealed the formation of hydrogen bonds during ligand-receptor interaction. ADMET exploration further validated the drug like properties of these compounds. Conclusion:: Present study revealed that active constituents of Azadirachta indica and Salvia officinalis can be potentially used to target SARS-CoV-2 by hindering its replication process.

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