scholarly journals Computational study of some potential inhibitors of COVID-19: A DFT analysis

2022 ◽  
Vol 0 (0) ◽  
pp. 0
Keyword(s):  
Computational Study ◽  
Potential Inhibitors

scholarly journals Combinatorial Library Designing and Virtual Screening of Cryptolepine Derivatives against Topoisomerase II by Molecular Docking

2020 ◽  
Author(s):  
Maria ◽  
Zahid Khan
Keyword(s):  
Molecular Docking ◽  
Cell Division ◽  
Binding Energy ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Combinatorial Library ◽  
Topoisomerase Ii ◽  
Computational Study ◽  
Binding Energies ◽  
Potential Inhibitors

AbstractComputational approaches have emerging role for designing potential inhibitors against topoisomerase 2 for treatment of cancer. TOP2A plays a key role in DNA replication before cell division and thus facilitates the growth of cells. This function of TOP2A can be suppressed by targeting with potential inhibitors in cancer cells to stop the uncontrolled cell division. Among potential inhibitors cryptolepine is more selective and has the ability to intercalate into DNA, effectively block TOP2A and cease cell division in cancer cells. However, cryptolepine is non-specific and have low affinity, therefore, a combinatorial library was designed and virtually screened for identification of its derivatives with greater TOP2A binding affinities.A combinatorial library of 31114 derivatives of cryptolepine was formed and the library was virtually screened by molecular docking to predict the molecular interactions between cryptolepine derivatives and TOP2A taking cryptolepine as standard. The overall screening and docking approach explored all the binding poses of cryptolepine for TOP2A to calculate binding energy. The compounds are given database number 8618, 907, 147, 16755, and 8186 scored lowest binding energies of −9.88kcal/mol, −9.76kcal/mol, −9.75kcal/mol, −9.73kcal/mol, and −9.72kcal/mol respectively and highest binding affinity while cryptolepine binding energy is −6.09kcal/mol. The good binding interactions of the derivatives showed that they can be used as potent TOP2A inhibitors and act as more effective anticancer agents than cryptolepine itself. The interactions of derivatives with different amino acid residues were also observed. A comprehensive understanding of the interactions of proposed derivatives with TOP2A helped for searching more novel and potent drug-like molecules for anticancer therapy. This Computational study suggests useful references to understand inhibition mechanisms that will help in the modification of TOP2A inhibitors.

scholarly journals In Silico Investigation of Spice Molecules as Potent Inhibitor of SARS-CoV-2

2020 ◽  
Author(s):  
Janmejaya Rout ◽  
Bikash Chandra Swain ◽  
Umakanta Tripathy
Keyword(s):  
Infectious Disease ◽  
Small Molecules ◽  
Potent Inhibitor ◽  
Computational Study ◽  
Spike Protein ◽  
Lab Experiments ◽  
Main Protease ◽  
Wet Lab ◽  
Potential Inhibitors ◽  
Adme Property

<p>The severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is a novel infectious disease that is in rapid growth. Several trials are going on worldwide to find a solution for this pandemic. The viral replication can be blocked by inhibiting the SARS-CoV-2 spike protein (SARS-CoV-2 Spro), and the SARS-CoV-2 main protease (SARS-CoV-2 Mpro). The binding of potential small molecules to these proteins can possibly inhibit the replication and transcription of the virus. The spice molecules that are used in our food have the properties of antiviral, antifungal, and antimicrobial nature. As spice molecules are consumed in the diet, hence its antiviral properties against SARS-CoV-2 will benefit in a significant manner. Therefore, in this work, the blind molecular docking of 30 selected spice molecules (through ADME property screening) was performed for the identification of potential inhibitors for the Spro and Mpro of SARS-CoV-2. We found that all the molecules bind actively with the SARS-CoV-2 Spro and Mpro. However, the molecule, Piperine, is found to have the highest binding affinity among the 30 screened molecules. We anticipate immediate wet-lab experiments and clinical trials in support of this computational study might be helpful in inhibiting the SARS-CoV-2 virus.</p>

scholarly journals In Silico Investigation of Spice Molecules as Potent Inhibitor of SARS-CoV-2

2020 ◽  
Author(s):  
Janmejaya Rout ◽  
Bikash Chandra Swain ◽  
Umakanta Tripathy
Keyword(s):  
Infectious Disease ◽  
Small Molecules ◽  
Potent Inhibitor ◽  
Computational Study ◽  
Spike Protein ◽  
Lab Experiments ◽  
Main Protease ◽  
Wet Lab ◽  
Potential Inhibitors ◽  
Adme Property

<p>The severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is a novel infectious disease that is in rapid growth. Several trials are going on worldwide to find a solution for this pandemic. The viral replication can be blocked by inhibiting the SARS-CoV-2 spike protein (SARS-CoV-2 Spro), and the SARS-CoV-2 main protease (SARS-CoV-2 Mpro). The binding of potential small molecules to these proteins can possibly inhibit the replication and transcription of the virus. The spice molecules that are used in our food have the properties of antiviral, antifungal, and antimicrobial nature. As spice molecules are consumed in the diet, hence its antiviral properties against SARS-CoV-2 will benefit in a significant manner. Therefore, in this work, the blind molecular docking of 30 selected spice molecules (through ADME property screening) was performed for the identification of potential inhibitors for the Spro and Mpro of SARS-CoV-2. We found that all the molecules bind actively with the SARS-CoV-2 Spro and Mpro. However, the molecule, Piperine, is found to have the highest binding affinity among the 30 screened molecules. We anticipate immediate wet-lab experiments and clinical trials in support of this computational study might be helpful in inhibiting the SARS-CoV-2 virus.</p>

Combinatorial library design and virtual screening of cryptolepine derivatives against topoisomerase IIA by molecular docking and DFT studies

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Maria ◽  
Zahid Khan ◽  
Aleksey E. Kuznetsov
Keyword(s):  
Molecular Docking ◽  
Cell Division ◽  
Binding Energy ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Combinatorial Library ◽  
Computational Study ◽  
Binding Energies ◽  
Binding Affinities ◽  
Potential Inhibitors

Abstract Various computational approaches have received ever-growing role in the design of potential inhibitors of the topoisomerase 2 (TOP2A) for cancer treatment. TOP2A plays a key role in the deoxyribonucleic acid (DNA) replication before cell division and thus facilitates the growth of cells. This TOP2A function can be suppressed by targeting it with potential inhibitors in cancer cells to terminate the uncontrolled cell division. Among potential inhibitors, cryptolepine has higher selectivity along with the ability to intercalate into DNA, effectively blocking TOP2A and ceasing cell division in cancer cells. However, this compound has drawbacks of being nonspecific and possessing relatively low affinity. Therefore, a combinatorial library of 31,114 cryptolepine derivatives was designed and virtually screened by molecular docking to predict the molecular interactions between the cryptolepine derivatives and TOP2A using cryptolepine as a standard. All the binding poses of cryptolepine derivatives for TOP2A were investigated to calculate binding energy. The compounds with the database numbers 8618, 907, 147, 16755, and 8186 scored the highest binding energies, −9.88, −9.76, −9.75, −9.73, and −9.72 kcal/mol, respectively, and the highest binding affinities while the cryptolepine binding energy is −6.09 kcal/mol. The strong binding interactions of these derivatives show that they can be used as potent TOP2A inhibitors and act as more effective anticancer agents than cryptolepine itself. The interactions of these derivatives with different amino acid residues were also observed and analyzed. A comprehensive understanding of the interactions of the proposed derivatives with TOP2A helped for searching more novel and potent drug-like molecules for anticancer therapy. This computational study suggests useful references to understand inhibition mechanisms that will help in the further modifications of TOP2A inhibitors. Moreover, the DFT study of the derivatives with the highest binding energies was performed, helping to further understand the binding affinities of these compounds.

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.

scholarly journals Novel Natural Inhibitors Targeting AKT1 by Computational Study

2021 ◽  
Author(s):  
Bo Wu ◽  
Wenzhuo Yang ◽  
Zhiyun Zhang ◽  
Gaojing Dou ◽  
Xiaye Lv ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Computational Study ◽  
Developmental Toxicity ◽  
Inhibitory Effect ◽  
Dynamics Simulation ◽  
Drug Candidates ◽  
Receptor Complexes ◽  
Zinc Database ◽  
Dynamics Simulations ◽  
Potential Inhibitors

Abstract Object: This study was designed to screen ideal lead compounds and drug candidates with an inhibitory effect on AKT1 from the drug library (ZINC database).Methods: A battery of computer-aided virtual techniques were used to identify potential inhibitors of AKT1. LibDock is used for structure-based screening followed by ADME (absorption distribution, metabolic excretion) and toxicity prediction. Molecular dynamics simulations were used to evaluate the stability of ligand-receptor complexes.Results: Two new natural compounds ZINC000049872065 and ZINC000021992902 were found to bind to AKT1 in the ZINC database, showing a higher binding affinity. Also, they were predicted to have lower rodent carcinogenicity, Ames mutagenicity, developmental toxicity potential, and high tolerance to cytochrome P4502D6. Molecular dynamics simulation shows that ZINC000049872065 and ZINC000021992902 have more favorable potential energies with AKT1, which can exist stably in the natural environment.Conclusion: This study suggests that ZINC000049872065 and ZINC000021992902 are ideal potential inhibitors of AKT1 targeting. These compounds are safe drug candidates and have important implications for the design and improvement of C-MET target drugs.

scholarly journals Computational Study on Novel Natural Inhibitors Targeting BCL2

2021 ◽  
Author(s):  
Xiaye Lv ◽  
Yuting Jiang ◽  
Xinhui Wang ◽  
Gaojing Dou ◽  
Jing Wang ◽  
...  
Keyword(s):  
Computational Study ◽  
Developmental Toxicity ◽  
B Cell Lymphoma ◽  
Inhibitory Effect ◽  
Dynamics Simulation ◽  
Lead Compounds ◽  
Toxicity Potential ◽  
Zinc Database ◽  
Potential Inhibitors ◽  
New Compounds

Abstract Object: Ideal lead compounds and candidate drugs with inhibitory effect on BCL2 were screened from ZINC database, which laid a foundation for drug development and compound improvement of drug treatment for diffuse large B-cell lymphoma (DLCBL). Methods: Identification of potential BCL2 inhibitors by computer-aided virtual screening. Libdock was applied to value 17931 compounds and top20 were selected for further analysis. Selected compounds were performed absorption, distribution, metabolism, and excretion (ADME) and toxicity prediction. The binding affinity between the selected ligands and BCL2 was confirmed by Molecular docking. Results: The new natural compounds ZINC00000255131 and ZINC00013298233 were found to bind closely with BCL2. Furthermore, they all scored lower in ames-induced mutagenicity, rodent carcinogenicity, non-developmental toxicity potential, and cytochrome P4502D6 tolerance. Molecular dynamics simulation shows that the combinations of ZINC00000255131 and ZINC00013298233 with BCL2 in the natural environment are more stable. Conclusion: Two new compounds ZINC00000255131 and ZINC00013298233 were found to be potential inhibitors of BCL2. These compounds have been proved to be safe, which is of great significance for the development and improvement of DLCBL drugs.

scholarly journals Computational study on novel natural inhibitors targeting BCL2

2021 ◽  
Vol 38 (8) ◽  
Author(s):  
Xiaye Lv ◽  
Yuting Jiang ◽  
Xinhui Wang ◽  
HaoQun Xie ◽  
Gaojing Dou ◽  
...  
Keyword(s):  
Computational Study ◽  
Developmental Toxicity ◽  
B Cell Lymphoma ◽  
Inhibitory Effect ◽  
Dynamics Simulation ◽  
Lead Compounds ◽  
Toxicity Potential ◽  
Zinc Database ◽  
Potential Inhibitors ◽  
New Compounds

AbstractIdeal lead compounds and candidate drugs with inhibitory effect on BCL2 were screened from ZINC database, which laid a foundation for drug development and compound improvement of drug treatment for diffuse large B-cell lymphoma (DLCBL). Identification of potential BCL2 inhibitors by computer-aided virtual screening. Libdock was applied to 17,931 compounds and the top 20 were selected for further analysis. Selected compounds were performed absorption, distribution, metabolism, and excretion (ADME) and toxicity prediction. The binding affinity between the selected ligands and BCL2 was confirmed by Molecular docking. The new natural compounds, ZINC00000255131 and ZINC00013298233, were found to bind closely with BCL2. Furthermore, they all scored lower in ames-induced mutagenicity, rodent carcinogenicity, non-developmental toxicity potential, and cytochrome P4502D6 tolerance. Molecular dynamics simulation shows that the combinations of ZINC00000255131 and ZINC00013298233 with BCL2 in the natural environment are more stable. Two new compounds, ZINC00000255131 and ZINC00013298233, were found to be potential inhibitors of BCL2. These compounds have been proved to be safe, which is of great significance for the development and improvement of DLCBL drugs.

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