Spleen Tyrosine Kinase as a Target Therapy for &lt;b&gt;&lt;i&gt;Pseudomonas aeruginosa&lt;/i&gt;&lt;/b&gt; Infection

Alhazmi, Alaa

doi:10.1159/000489863

Cited by 15 publications

(17 citation statements)

References 109 publications

(102 reference statements)

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“…Fostamatinib is an inhibitor of spleen tyrosine kinase Syk proteinand an immune-modulator.It is used in the treatment of immunethrombocytopenicpurpura (ITP). In immunocompromised individuals, chronic lung infection could be prevented by inhibition of Syk by using Fostamatinib 35 . During infection, virus induced huge cytokine enhancement could be regulated by the Fostamatinib induced inhibition of Syk.…”

Section: Docking With Cefpiramide (Pubchem Cid:636405)mentioning

confidence: 99%

In-silico analysis of potential interaction of drugs and the SARS-CoV-2 spike protein

Bank

Basak

Girish³

et al. 2020

Preprint

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The world is suffering its deadly pandemic in decades from Corona virus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Till the end of April, 2020, the death toll rose to more than 2 lacs worldwide (224 301, on May 1st), affecting 215 countries (source: WHO). Since the invention of a new drug or vaccine takes time, drug repurposing is one of the avenues. Keeping that in mind, we have tried to shed light on some of the drugs, using molecular docking/modeling studies, which could be of immense importance in the current scenario. Using bioinformatic approaches, we have tried to work on the viral spike (S) protein, majorly involved in pathogenicity through its receptor binding event and fusion to the host cells. More emphasis was given on the spike proteins (6vsb) and (6lxt). We predicted the drugs that target to the S proteins by in-silico docking analysis. We determined the functional part of the spike of SARS-CoV-2 and the drugs were predicted by analysis of the functional part using the PDBsum/DrugPort. Molecular Docking unveiled the binding of those drugs to the target spike. This in-silico study actually envisions the efficacy of the predicted drugs against the spikes of SARS-CoV-2 and the binding of the drugs might propose the combinatorial effect of the drugs to neutralize the spike effect in the human body.

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Section: Docking With Cefpiramide (Pubchem Cid:636405)mentioning

confidence: 99%

In-silico analysis of potential interaction of drugs and the SARS-CoV-2 spike protein

Bank

Basak

Girish³

et al. 2020

Preprint

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“…Thus, non-receptor tyrosine kinases must be closely linked to TLR activation [ 29 ]. Syk kinase is an important component of PRR signalling and through it a multitude of signal cascades are activated, including the MAP kinases and NF-κB [ 30 ]. Recently, the use of the Syk inhibitor R406 has been shown to inhibit p38MAPK and ERK phosphorylation, as well as reducing inflammatory cytokine release from human monocyte cells [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Pseudomonas aeruginosa induces p38MAP kinase-dependent IL-6 and CXCL8 release from bronchial epithelial cells via a Syk kinase pathway

et al. 2021

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Pseudomonas aeruginosa (Pa) infection is a major cause of airway inflammation in immunocompromised and cystic fibrosis (CF) patients. Mitogen-activated protein (MAP) and tyrosine kinases are integral to inflammatory responses and are therefore potential targets for novel anti-inflammatory therapies. We have determined the involvement of specific kinases in Pa-induced inflammation. The effects of kinase inhibitors against p38MAPK, MEK 1/2, JNK 1/2, Syk or c-Src, a combination of a p38MAPK with Syk inhibitor, or a novel narrow spectrum kinase inhibitor (NSKI), were evaluated against the release of the proinflammatory cytokine/chemokine, IL-6 and CXCL8 from BEAS-2B and CFBE41o- epithelial cells by Pa. Effects of a Syk inhibitor against phosphorylation of the MAPKs were also evaluated. IL-6 and CXCL8 release by Pa were significantly inhibited by p38MAPK and Syk inhibitors (p<0.05). Phosphorylation of HSP27, but not ERK or JNK, was significantly inhibited by Syk kinase inhibition. A combination of p38MAPK and Syk inhibitors showed synergy against IL-6 and CXCL8 induction and an NSKI completely inhibited IL-6 and CXCL8 at low concentrations. Pa-induced inflammation is dependent on p38MAPK primarily, and Syk partially, which is upstream of p38MAPK. The NSKI suggests that inhibiting specific combinations of kinases is a potent potential therapy for Pa-induced inflammation.

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“…Pseudomonas aeruginosa is an opportunistic Gramnegative bacterium, which is responsible for systemic infections among immunocompromised patients (1). This organism poses a growing public health concern worldwide.…”

Section: Introductionmentioning

confidence: 99%

Poor Antimicrobial Activity of Opium Against Carbapenem-Resistant Pseudomonas aeruginosa Isolates

Khajooee

Shoja

2020

Gene Cell Tissue

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Background: Carbapenem-resistant Pseudomonas aeruginosa (P. aeruginosa) has dramatically increased. Thus, finding a new therapeutic option is necessary to fight such isolates. Objectives: This study aimed to explore the influence of opium on carbapenem-resistant and carbapenem-sensitive P. aeruginosa. Methods: During the study period from December 2018 to March 2019, a total of 20 non-duplicate P. aeruginosa isolates were collected from clinical samples in Shahid Mohammadi and Pediatrics hospitals (teaching hospitals) affiliated to Hormozgan University of Medical Sciences in Bandar Abbas, the South of Iran. The antimicrobial susceptibility pattern was tested by the disc diffusion method according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The influence of opium was tested by broth microdilution and agar disc diffusion methods against P. aeruginosa isolates. Results: We studied 20 isolates of P. aeruginosa, of which 30%, 30%, 15%, 10%, 10%, and 5% were collected from wound, urine, discharge, blood, tracheal tube, and other specimens, respectively. According to the antimicrobial susceptibility testing results, the highest and lowest rates of resistance were to ofloxacin and piperacillin, respectively. Unexpectedly, all clinical and standard isolates of P. aeruginosa were resistant to different concentrations of opium. Conclusions: Based on our experiments, no antimicrobial effect was found for opium against the tested isolates. Studies of opium need to be continued as it may show some bacteriostatic or bactericide activities in other conditions.

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Spleen Tyrosine Kinase as a Target Therapy for <b><i>Pseudomonas aeruginosa</i></b> Infection

Cited by 15 publications

References 109 publications

In-silico analysis of potential interaction of drugs and the SARS-CoV-2 spike protein

In-silico analysis of potential interaction of drugs and the SARS-CoV-2 spike protein

Pseudomonas aeruginosa induces p38MAP kinase-dependent IL-6 and CXCL8 release from bronchial epithelial cells via a Syk kinase pathway

Poor Antimicrobial Activity of Opium Against Carbapenem-Resistant Pseudomonas aeruginosa Isolates

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