Structure-based virtual screening to identify inhibitors against Staphylococcus aureus MurD enzyme

Azam, Mohammed Afzal; Jupudi, Srikanth

doi:10.1007/s11224-019-01330-z

Cited by 10 publications

(6 citation statements)

References 49 publications

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“…(Kumar et al, 2019a; V. K. S. Vishvakarma, N.; Reetu; Kumari, K.; Patel R.; Singh, P., 2019) Sum of the energy-related to corresponding interaction will to leads to the total binding energy and act as a marker for particular noscapines regarding their potential against the protease of SARS-CoV-2. (Azam & Jupudi, 2019) Based on the total binding energy, noscapines were screened and arranged by their potential as given in Table 2. Further, 14 known compounds with different antiviral potential were taken from the database and our results were compared with the reported antiviral agents.…”

Section: Molecular Docking Resultsmentioning

confidence: 99%

Inhibition of Protease of Novel Corona Virus by Designed Noscapines: Molecular Docking and ADMET Studies

Vishvakarma¹,

Kumari²,

Singh

2020

Preprint

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<p>Nowadays, many people were dying due to infectious coronavirus diseases (COVID-19). It belongs to the betacoronavirus family and also known as SARS-CoV-2. However, COVID-19 is a new form that has some basic difference in the genome which makes it more lethal and infectious. In transmitted in human in late December 2019 and it infected about 20 million till date. Its genome is composed of positive-sense single-stranded RNA, which encodes for the poly-protein. This poly-protein further cleaved into various components of the virus to make the numerous copy of the virus. There are many more similarities in their genome among the SARS-CoV-2, SARS-CoV, MERS-CoV. However, protease proteins are responsible for the cleavage and hence, COVID-19 main protease is a prime therapeutic target. To date, no medicine/ vaccine can fully cure their infection. To inhibit the activity of protease of COVID-19, molecular docking and ADMET studies of 116 noscapine derivatives were performed and the result was compared with 14 reputed antiviral drugs including chloroquine and hydroxychloroquine. The molecular docking result indicates a better binding in comparison of 14 reputed drugs. Further, the top six noscapines was taken into consideration for the pose analysis and ADMET studies. Finally, the top six noscapine was refined by ADMET properties to get the most potent one.</p>

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Section: Molecular Docking Resultsmentioning

confidence: 99%

Inhibition of Protease of Novel Corona Virus by Designed Noscapines: Molecular Docking and ADMET Studies

Vishvakarma¹,

Kumari²,

Singh

2020

Preprint

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“…In this process, a series of enzymes are needed to synthesize new peptidoglycan, involving six MurA-F, PBPs family. These enzymes are attractive drug targets as it is essential and ubiquitous in bacteria but absent in mammalian cells (Azam and Jupudi, 2019). In addition, PBP1A, which catalyzes the transglycosylation and transpeptidation reactions is already the target of b-lactams antibiotics (Ali et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Proteomic and Metabolomic Analyses Provide Insights into the Mechanism on Arginine Metabolism Regulated by tRNA Modification Enzymes GidA and MnmE of Streptococcus suis

Gao¹,

Yuan²,

Liu³

et al. 2020

Front. Cell. Infect. Microbiol.

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GidA and MnmE, two important tRNA modification enzymes, are contributed to the addition of the carboxymethylaminomethyl (cmnm) group onto wobble uridine of tRNA. GidA-MnmE modification pathway is evolutionarily conserved among Bacteria and Eukarya, which is crucial in efficient and accurate protein translation. However, its function remains poorly elucidated in zoonotic Streptococcus suis (SS). Here, a gidA and mnmE double knock-out (DKO) strain was constructed to systematically decode regulatory characteristics of GidA-MnmE pathway via proteomic. TMT labelled proteomics analysis identified that many proteins associated with cell divison and growth, fatty acid biosynthesis, virulence, especially arginine deiminase system (ADS) responsible for arginine metabolism were down-regulated in DKO mutant compared with the wild-type (WT) SC19. Accordingly, phenotypic experiments showed that the DKO strain displayed decreased in arginine consumption and ammonia production, deficient growth, and attenuated pathogenicity. Moreover, targeted metabolomic analysis identified that arginine was accumulated in DKO mutant as well. Therefore, these data provide molecular mechanisms for GidA-MnmE modification pathway in regulation of arginine metabolism, cell growth and pathogenicity of SS. Through proteomic and metabolomic analysis, we have identified arginine metabolism that is the links between a framework of protein level and the metabolic level of GidA-MnmE modification pathway perturbation.

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“…All loops including seven nontemplate loops (Val12-Cys16, Trp64-Val68, Glu221-Leu223, Gly243-Val245, Leu346-Arg348 and Lys412-Asp417) of the generated model were refined using the OPLS3e force field and prime. Furthermore, the modelled protein was subjected to 50-ns MD simulation using Desmond software with the OPLS3e force field using the protocols described earlier [32]. The resultant protein was then optimized by the Protein Preparation Wizard [33] incorporated in Schrödinger Suite 2019-2.…”

Section: Homology Modellingmentioning

confidence: 99%

An explorative study on diarylquinoline-based inhibitor targeting Enterococcus faecium MurF

Azam

Manoj

2020

Struct Chem

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Enterococcus faecium MurF (EfMurF) enzyme catalyzes the addition of D-alanyl-D-alanine to form murein UDP-Nacetylmuramoyl-pentapeptide. This is the last cytoplasmic step of peptidoglycan synthesis and is essential for bacterial cell wall integrity. Due to the specificity of D-amino acid utilization and its absence in eukaryotic counterpart, this enzyme is considered as an attractive target for new antibacterial discovery. In the present investigation, we prepared the 3D structure of the EfMurF catalytic pocket by homology modelling. A combined molecular modelling approach was used to get insight into the binding mode of diarylquinoline-based inhibitor 1 against EfMurF. In extra-precision (XP) docking, inhibitor 1 exhibited hydrogen bonding and π-π stacking interactions mainly with the residues of N-terminal and central domains. In the molecular mechanics/generalized born surface area (MM-GBSA) binding free energy calculation, Coulomb and the non-polar solvation energy terms are observed to be major contributors for the inhibitor binding. To gain further insight into the binding mode and inhibition potential, the inhibitor 1/EfMurF enzyme complex was analyzed with 100-ns molecular dynamics simulation. Based on the docking and MD results, we designed three new compounds D1-D3 with a high binding affinity against EfMurF. These three designed compounds were subjected to the XP docking and the binding free energy calculation. A 50-ns MD simulation was also performed for the D1/EfMurF complex.

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Structure-based virtual screening to identify inhibitors against Staphylococcus aureus MurD enzyme

Cited by 10 publications

References 49 publications

Inhibition of Protease of Novel Corona Virus by Designed Noscapines: Molecular Docking and ADMET Studies

Inhibition of Protease of Novel Corona Virus by Designed Noscapines: Molecular Docking and ADMET Studies

Proteomic and Metabolomic Analyses Provide Insights into the Mechanism on Arginine Metabolism Regulated by tRNA Modification Enzymes GidA and MnmE of Streptococcus suis

An explorative study on diarylquinoline-based inhibitor targeting Enterococcus faecium MurF

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