Potential inhibitors of SARS-CoV-2 (COVID 19) proteases PLpro and Mpro/ 3CLpro: molecular docking and simulation studies of three pertinent medicinal plant natural components

Novel inhibitors designing against the potential drug target of Plasmodium falciparum M17 Leucyl Aminopeptidase - PfM17LAP

10.1101/2021.12.14.472562 ◽

2021 ◽

Author(s):

Govinda Rao Dabburu ◽

Manish Kumar ◽

Naidu Subbarao

Keyword(s):

Plasmodium Falciparum ◽

Molecular Docking ◽

Drug Target ◽

Docking Studies ◽

Simulation Studies ◽

Docking Analysis ◽

Discovery Studio ◽

Potential Inhibitors ◽

Key Words Malaria ◽

Leucyl Aminopeptidase

Abstract: Malaria is one of the major disease of concern worldwide especially in the African regions. According to the recent WHO reports, African regions share 95% of the total deaths worldwide that occurs due to malaria. Plasmodium falciparum M17 Leucyl Aminopeptidase (PfM17LAP) plays an important role in the regulation of amino acids release and for the survival of the parasite. We performed molecular docking and simulation studies to find the potential inhibitors against PfM17LAP using ChEMBL antimalarial library. Molecular docking studies and post-docking analysis revealed that molecules CHEMBL369831 and CHEMBL176888 showed better binding than the reference molecule BESTATIN. LibDock and X-SCORES of molecules BES, CHEMBL369831 and CHEMBL176888 are 130.071, 230.38, 223.56 and -8.75 Kcal/mol, -10.90 Kcal/mol, -11.05 Kcal/mol respectively. ADMET profiling of the top ten ranked molecules was done by using the Discovery Studio. Molecular dynamic studies revealed that the complex PfM17LAP-CHEMBL369831 is stable throughout the simulation. Finally, we have reported novel inhibitors which possess more binding affinity towards PfM17LAP. Key words: Malaria, M17 Leucyl Aminopeptidase, ADMET, X-SCORE

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In silico identification of potential inhibitors against main protease of SARS-CoV-2 6LU7 from Andrographis panniculata via molecular docking, binding energy calculations and molecular dynamics simulation studies

Saudi Journal of Biological Sciences ◽

10.1016/j.sjbs.2021.10.060 ◽

2021 ◽

Author(s):

Mayakrishnan Vijayakumar ◽

Balakarthikeyan Janani ◽

Priya Kannappan ◽

Senthil Renganathan ◽

Sameer Al-Ghamdi ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Molecular Dynamics Simulation ◽

Binding Energy ◽

Dynamics Simulation ◽

Simulation Studies ◽

Main Protease ◽

In Silico Identification ◽

Potential Inhibitors ◽

Binding Energy Calculations

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Exploration of potential inhibitors for tuberculosis via structure‐based drug design, molecular docking, and molecular dynamics simulation studies

Journal of Computational Chemistry ◽

10.1002/jcc.26712 ◽

2021 ◽

Author(s):

Sreerama Rajasekhar ◽

Ramanathan Karuppasamy ◽

Kaushik Chanda

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Molecular Dynamics Simulation ◽

Drug Design ◽

Dynamics Simulation ◽

Simulation Studies ◽

Structure Based Drug Design ◽

Potential Inhibitors

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Screening Malaria-box compounds to identify potential inhibitors against SARS-CoV-2 Mpro, using molecular docking and dynamics simulation studies

European Journal of Pharmacology ◽

10.1016/j.ejphar.2020.173664 ◽

2021 ◽

Vol 890 ◽

pp. 173664

Author(s):

Shahzaib Ahamad ◽

Hema Kanipakam ◽

Shweta Birla ◽

Md Shaukat Ali ◽

Dinesh Gupta

Keyword(s):

Molecular Docking ◽

Dynamics Simulation ◽

Simulation Studies ◽

Potential Inhibitors ◽

Molecular Docking And Dynamics ◽

Malaria Box

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qNMR quantification and in silico analysis of isobrucein B and neosergeolide from Picrolemma sprucei as potential inhibitors of SARS-CoV-2 protease (3CLpro) and RNA-dependent RNA polymerase (RdRp) and pharmacokinetic and toxicological properties

Research Society and Development ◽

10.33448/rsd-v10i16.23220 ◽

2021 ◽

Vol 10 (16) ◽

pp. e69101623220

Author(s):

Marcos Túlio da Silva ◽

Matheus Gabriel de Oliveira ◽

José Realino de Paula ◽

Vinicius Barreto da Silva ◽

Kidney de Oliveira Gomes Neves ◽

...

Keyword(s):

Molecular Docking ◽

Medicinal Plant ◽

In Silico ◽

Active Sites ◽

In Silico Analysis ◽

In Vivo Experiments ◽

Inhibitory Potential ◽

Potential Inhibitors

Objective: To quantify the quassinoids of P. sprucei, a medicinal plant that is native to the Amazon region, using qNMR and investigate the inhibitory potential of isobrucein B and neosergeolide on the 3CLpro and RdRp targets of SARS-CoV-2 through in silico approaches. Methods: the quantification was performed in a fraction (F2-F3) enriched with the quassinoids isobrucein B and neosergeolide using the PULCON method. In silico assays were performed using molecular docking to assess interactions and binding affinity between neosergeolide and isobrucein B ligands with SARS-CoV-2 3CLpro and RdRp targets, and online servers were used to estimate pharmacokinetic and toxicity. Results: It was possible to determine the quantity of the two quassinoids isobrucein B and neosergeolide in the F2-F3 fraction (769.6 mg), which were present in significant amounts in the PsMeOH extract (5.46%). The results of the docking analysis, based on the crystallized structures of RdRp and 3CLpro, indicated that isobrucein B and neosergeolide are potential inhibitors of the two proteins evaluated, as well as showing the importance of hydrogen bonding and pi (π) interactions for the active sites foreseen for each target. Conclusion: The results suggest that P. sprucei quassinoids may interact with 3CLpro and RdRp targets. In vitro and in vivo experiments are needed to confirm the results of molecular docking and investigate the risks of using P. sprucei as a medicinal plant against COVID-19.

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