In-Silico Repurposing of Anticancer Drug (5-FU) as an Antimicrobial Agent Against Methicillin-Resistant Staphylococcus aureus (MRSA)

2020 ◽  
Vol 26 (4) ◽  
pp. 2137-2145
Author(s):  
Amey Sharma ◽  
Avani Sharma ◽  
Apoorva Rana ◽  
Ravi Ranjan Kumar Niraj
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agent ◽  
Anticancer Drug ◽  
In Silico ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistant

Synthesis and structural studies of 1-phenyl-1,3-butanedione copper(II) complexes as an excellent antimicrobial agent against methicillin-resistant Staphylococcus aureus

2019 ◽  
Vol 484 ◽  
pp. 227-236 ◽  
Author(s):  
Hema M. Krishnegowda ◽  
Chimatahalli S. Karthik ◽  
Manukumar H. Marichannegowda ◽  
Karthik Kumara ◽  
Pampa J. Kudigana ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agent ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Structural Studies ◽  
Methicillin Resistant

scholarly journals Inhibition and Biochemical Characterization of Methicillin-Resistant Staphylococcus aureus Shikimate Dehydrogenase: An in Silico and Kinetic Study

Molecules ◽  
2014 ◽  
Vol 19 (4) ◽  
pp. 4491-4509 ◽  
Author(s):  
Claudia Avitia-Domínguez ◽  
Erick Sierra-Campos ◽  
José Salas-Pacheco ◽  
Hugo Nájera ◽  
Arturo Rojo-Domínguez ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Kinetic Study ◽  
In Silico ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Biochemical Characterization ◽  
Shikimate Dehydrogenase ◽  
Methicillin Resistant

Design and in silico analysis of a whole‐cell biosensor able to kill methicillin‐resistant Staphylococcus aureus

2021 ◽  
Author(s):  
Diego Francisco Benítez‐Chao ◽  
Francisco de Jesús Balderas‐Cisneros ◽  
Angel León‐Buitimea ◽  
José Rubén Morones‐Ramírez
Keyword(s):  
Staphylococcus Aureus ◽  
In Silico ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
In Silico Analysis ◽  
Whole Cell ◽  
Methicillin Resistant ◽  
Whole Cell Biosensor ◽  
Silico Analysis ◽  
Cell Biosensor

scholarly journals Non-β-Lactam Allosteric Inhibitors Target Methicillin-Resistant Staphylococcus aureus: An In Silico Drug Discovery Study

Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 934
Author(s):  
Mahmoud A. A. Ibrahim ◽  
Khlood A. A. Abdeljawaad ◽  
Alaa H. M. Abdelrahman ◽  
Othman R. Alzahrani ◽  
Fahad M. Alshabrmi ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
In Silico ◽  
Acidic Medium ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Binding Affinities ◽  
Allosteric Site ◽  
Allosteric Inhibitors ◽  
Methicillin Resistant ◽  
In Silico Admet

Penicillin-binding proteins (PBPs) catalyze the final stages for peptidoglycan cell-wall bio-synthesis. Mutations in the PBP2a subunit can attenuate β-lactam antibiotic activity, resulting in unimpeded cell-wall formation and methicillin-resistant Staphylococcus aureus (MRSA). A double mutation in PBP2a (i.e., N146K and E150K) is resistant to β-lactam inhibitors; however, (E)-3-(2-(4-cyanostyryl)-4-oxoquinazolin-3(4H)-yl) benzoic acid (QNZ), a heterocyclic antibiotic devoid of a β-lactam ring, interacts non-covalently with PBP2a allosteric site and inhibits PBP enzymatic activity. In the search for novel inhibitors that target this PBP2a allosteric site in acidic medium, an in silico screening was performed. Chemical databases including eMolecules, ChEMBL, and ChEBI were virtually screened for candidate inhibitors with a physicochemical similarity to QNZ. PBP2a binding affinities from the screening were calculated based on molecular docking with co-crystallized ligand QNZ serving as a reference. Molecular minimization calculations were performed for inhibitors with docking scores lower than QNZ (calc. −8.3 kcal/mol) followed by combined MD simulations and MM-GBSA binding energy calculations. Compounds eMol26313223 and eMol26314565 exhibited promising inhibitor activities based on binding affinities (ΔGbinding) that were twice that of QNZ (−38.5, −34.5, and −15.4 kcal/mol, respectively). Structural and energetic analyses over a 50 ns MD simulation revealed high stability for the inhibitors when complexed with the double mutated PBP2a. The pharmacokinetic properties of the two inhibitors were predicted using an in silico ADMET analysis. Calculated binding affinities hold promise for eMol26313223 and eMol26314565 as allosteric inhibitors of PBP2a in acidic medium and establish that further in vitro and in vivo inhibition experimentation is warranted.

scholarly journals Identification of an Antimicrobial Agent Effective against Methicillin-Resistant Staphylococcus aureus Persisters Using a Fluorescence-Based Screening Strategy

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0127640 ◽  
Author(s):  
Wooseong Kim ◽  
Annie L. Conery ◽  
Rajmohan Rajamuthiah ◽  
Beth Burgwyn Fuchs ◽  
Frederick M. Ausubel ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agent ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Screening Strategy ◽  
Methicillin Resistant
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