Pharmacoinformatics-based identification of anti-bacterial catalase-peroxidase enzyme inhibitors

Jangam, Chaitanya Sadashiv; Bhowmick, Shovonlal; Chorge, Rekha Dhondiram; Bharatrao, Lomate Dhanraj; Patil, Pritee Chunarkar; Chikhale, Rupesh; AlFaris, Nora A.; AlTamimi, Jozaa Z.; Wabaidur, Saikh Mohammad; Islam, Ataul

doi:10.1016/j.compbiolchem.2019.107136

Cited by 16 publications

(13 citation statements)

References 53 publications

(70 reference statements)

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“…The RMSD, docking score, Glide score, and binding energy were recorded for each molecule (Kerzare et al, 2016). The Virtual Screening Workflow (VSW) available on the Schrodinger suite is a grid-based ligand docking with energetics module (Friedrich et al, 2017;Jangam et al, 2019). The VSW was used for the rigorous screening, docking, and validation studies of the natural product dataset.…”

Section: Molecular Docking and Virtual Screening Workflowmentioning

confidence: 99%

Identification of potential anti-TMPRSS2 natural products through homology modelling, virtual screening and molecular dynamics simulation studies

Chikhale

Gupta

Eldesoky

et al. 2020

Journal of Biomolecular Structure and Dynamics

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Recent outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a pandemic of COVID-19. The absence of a therapeutic drug and vaccine is causing severe loss of life and economy worldwide. SARS-CoV and SARS-CoV-2 employ the host cellular serine protease TMPRSS2 for spike (S) protein priming for viral entry into host cells. A potential way to reduce the initial site of SARS-CoV-2 infection may be to inhibit the activity of TMPRSS2. In the current study, the three-dimensional structure of TMPRSS2 was generated by homology modelling and subsequently validated with a number of parameters. The structure-based virtual screening of Selleckchem database was performed through 'Virtual Work Flow' (VSW) to find out potential lead-like TMPRSS2 inhibitors. Camostat and bromhexine are known TMPRSS2 inhibitor drugs, hence these were used as control molecules throughout the study. Based on better dock score, binding-free energy and binding interactions compared to the control molecules, six molecules (Neohesperidin, Myricitrin, Quercitrin, Naringin, Icariin, and Ambroxol) were found to be promising against the TMPRSS2. Binding interactions analysis revealed a number of significant binding interactions with binding site amino residues of TMPRSS2. The all-atoms molecular dynamics (MD) simulation study indicated that all proposed molecules retain inside the receptor in dynamic states. The binding energy calculated from the MD simulation trajectories also favour the strong affinity of the molecules towards the TMPRSS2. Proposed molecules belong to the bioflavonoid class of phytochemicals and are reported to possess antiviral activity, our study indicates their possible potential for application in COVID-19.

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Section: Molecular Docking and Virtual Screening Workflowmentioning

confidence: 99%

Identification of potential anti-TMPRSS2 natural products through homology modelling, virtual screening and molecular dynamics simulation studies

Chikhale

Gupta

Eldesoky

et al. 2020

Journal of Biomolecular Structure and Dynamics

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“…As such, developing small molecules or other chemotherapeutic strategies to inhibit these enzymes may be a viable option to defend against these bacterial infections. The identification of these bacterium-specific inhibitors is being researched currently and includes small molecules that inhibit M. tuberculosis catalase ( 78 ). A plausible future direction of our work may include screening preexisting banks of small molecules against purified GBS NADH peroxidase protein or creating a crystal structure to identify regions for targeted drug design.…”

Section: Discussionmentioning

confidence: 99%

Streptococcus agalactiae npx Is Required for Survival in Human Placental Macrophages and Full Virulence in a Model of Ascending Vaginal Infection during Pregnancy

Moore

Spicer

et al. 2022

mBio

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This study sheds new light on the way that group B Streptococcus (GBS) defends itself against oxidative stress in the infected host. The enzyme encoded by the GBS gene npx is an NADH peroxidase that, our study reveals, provides defense against macrophage-derived reactive oxygen stress and facilitates infections of the uterus during pregnancy. This enzyme could represent a tractable target for future treatment strategies against invasive GBS infections.

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“…As such, developing small molecules or other chemotherapeutic strategies to inhibit these enzymes may be viable option to defend against these bacterial infections. Identification of these bacteria-specific inhibitors are being researched currently and include small molecules which inhibit M. tuberculosis catalase (84). A plausible future direction of our work may include screening pre-existing banks of small molecules against purified GBS NADH peroxidase protein or creating a crystal structure to identify regions for targeted drug design.…”

Section: Discussionmentioning

confidence: 99%

Streptococcus agalactiae npxis required for survival in human placental macrophages and full virulence in a model of ascending vaginal infection during pregnancy

Gaddy

2022

Preprint

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Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is a Gram-positive encapsulated bacterium that colonizes the gastrointestinal tract of 30-50% of humans. GBS causes invasive infection during pregnancy that can lead to chorioamnionitis, funisitis, preterm prelabor rupture of membranes (PPROM), preterm birth, neonatal sepsis, and maternal and fetal demise. Upon infecting the host, GBS encounters sentinel innate immune cells, such as macrophages, within reproductive tissues. Once phagocytosed by macrophages, GBS upregulates expression of the gene, npx, which encodes a NADH peroxidase. GBS mutants with a npx deletion (Δnpx) are exquisitely sensitive to reactive oxygen stress. Furthermore, we have shown that npx is required for GBS survival in both THP-1 and placental macrophages. In an in vivo murine model of ascending GBS vaginal infection during pregnancy, npx is required for invasion of reproductive tissues and is critical for inducing disease progression including PPROM and preterm birth. Reproductive tissue cytokine production was also significantly diminished in Δnpx infected animals compared to those infected with wild type (WT)-GBS. Complementation in trans reversed this phenotype, indicating npx is critical for GBS survival and initiation of proinflammatory signaling in the gravid host.

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Pharmacoinformatics-based identification of anti-bacterial catalase-peroxidase enzyme inhibitors

Cited by 16 publications

References 53 publications

Identification of potential anti-TMPRSS2 natural products through homology modelling, virtual screening and molecular dynamics simulation studies

Identification of potential anti-TMPRSS2 natural products through homology modelling, virtual screening and molecular dynamics simulation studies

Streptococcus agalactiae npx Is Required for Survival in Human Placental Macrophages and Full Virulence in a Model of Ascending Vaginal Infection during Pregnancy

Streptococcus agalactiae npxis required for survival in human placental macrophages and full virulence in a model of ascending vaginal infection during pregnancy

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