Effects of BTK signalling in pathogenic microorganism infections

Ye, Bingjue; Zhou, Cheng; Guo, Huiting; Zheng, Min

doi:10.1111/jcmm.14548

Cited by 29 publications

(19 citation statements)

References 65 publications

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“…studies have confirmed the role of BTK in monocyte/macrophage and neutrophil activity(49,50), which contribute to the inflammatory response to infections. A study that examined lungs of COVID-19 patients confirmed that the infiltrate of immune cells in alveoli were majorly macrophages and monocytes, while moderate multinucleated giant cells, minimal lymphocytes, eosinophils and neutrophils were also observed(51).…”

mentioning

confidence: 77%

Relevance of the Bruton Tyrosine Kinase as a Target for COVID-19 Therapy

Rada¹,

Qusairy

Massip-Salcedo

et al. 2020

Molecular Cancer Research

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The outbreak of the novel coronavirus disease 2019 has emerged as one of the biggest global health threats worldwide. As of October 2020, over 44 million confirmed cases and more than 1,160,000 deaths have been reported globally, and the toll is likely to be much higher before the pandemic is over. There are currently little therapeutic options available and new potential targets are intensively investigated. Recently, Bruton Tyrosine Kinase (BTK) has emerged as an interesting candidate. Elevated levels of BTK activity have been reported in blood monocytes from patients with severe COVID-19, compared to those from healthy volunteers. Importantly, various studies confirmed empirically that administration of BTK inhibitors (Acalabrutinib and Ibrutinib) decreased the duration of mechanical ventilation and mortality rate for hospitalized patients with severe COVID-19. Herein, we review the current information regarding the role of BTK in SARS-CoV-2 infections and the suitability of its inhibitors as drugs to treat COVID-19. Implications:The use of BTK inhibitors in the management of COVID-19 shows promise in reducing the severity of the immune response to the infection and thus mortality. However, BTK inhibition may be contributing in other ways to inhibit the effects of the virus and this will need to be carefully studied.

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mentioning

confidence: 77%

Relevance of the Bruton Tyrosine Kinase as a Target for COVID-19 Therapy

Rada¹,

Qusairy

Massip-Salcedo

et al. 2020

Molecular Cancer Research

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“…This finding supports the suggested anti-inflammatory effect of BTK inhibitors in the lung. Similar studies have also revealed the role of BTK in neutrophil and macrophage/monocyte activity [ 60 , 61 ], which contribute to the inflammatory response to infections.…”

Section: The Role Of Btk Inhibitors In the Treatment Of Covid-19mentioning

confidence: 68%

Bruton tyrosine kinase inhibitors as potential therapeutic agents for COVID-19: A review

Kifle¹

2021

Metabolism Open

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Coronavirus disease 2019 (COVID-19) is first detected in December 2019 in Wuhan, China which is a new pandemic caused by SARS-COV-2 that has greatly affected the whole world. Bruton tyrosine kinase (BTK) inhibitors are drugs that are used for the management of cancer, and are being repurposed for COVID-19. BTK regulates macrophage and B cell activation, development, survival, and signaling. Inhibition of BTK has revealed an ameliorative effect on lung injury in patients with severe COVID-19. Thus, this review aimed to summarize evidence regarding the role of Bruton tyrosine kinase inhibitors against COVID-19. To include findings from diverse studies, publications related to BTK inhibitors and Covid-19 were searched from the databases such as SCOPUS, Web of Science, Medline, Google Scholar, PubMed, and Elsevier, using English key terms. Both experimental and clinical studies suggest that targeting excessive host inflammation with a BTK inhibitor is a potential therapeutic strategy in the treatment of patients with severe COVID-19. Currently, BTK inhibitors such as ibrutinib and acalabrutinib have shown a protective effect against pulmonary injury in a small series group of COVID-19 infected patients. Small molecule inhibitors like BTK inhibitors, targeting a wide range of pro-inﬂammatory singling pathways, may a key role in the management of COVID-19.

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“…In general, BTK signaling regulates downstream B cell receptor, Fc receptor and TLR7/8/3 signaling pathways. The inhibition of BTK could elevate the type I interferon levels and activate TLR signaling in systemic lupus erythematosus and different experimental models [34][35][36][37]. Another study reported that blocking the BTK, TLR3-induced protein kinase B (Akt), mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB signaling pathways enhanced the antiviral responses in mice models [38].…”

Section: Discussionmentioning

confidence: 99%

Structure-Based Virtual Screening Reveals Ibrutinib and Zanubrutinib as Potential Repurposed Drugs against COVID-19

Kaliamurthi

Selvaraj

et al. 2021

IJMS

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Coronavirus disease (COVID)-19 is the leading global health threat to date caused by a severe acute respiratory syndrome coronavirus (SARS-CoV-2). Recent clinical trials reported that the use of Bruton’s tyrosine kinase (BTK) inhibitors to treat COVID-19 patients could reduce dyspnea and hypoxia, thromboinflammation, hypercoagulability and improve oxygenation. However, the mechanism of action remains unclear. Thus, this study employs structure-based virtual screening (SBVS) to repurpose BTK inhibitors acalabrutinib, dasatinib, evobrutinib, fostamatinib, ibrutinib, inositol 1,3,4,5-tetrakisphosphate, spebrutinib, XL418 and zanubrutinib against SARS-CoV-2. Molecular docking is conducted with BTK inhibitors against structural and nonstructural proteins of SARS-CoV-2 and host targets (ACE2, TMPRSS2 and BTK). Molecular mechanics-generalized Born surface area (MM/GBSA) calculations and molecular dynamics (MD) simulations are then carried out on the selected complexes with high binding energy. Ibrutinib and zanubrutinib are found to be the most potent of the drugs screened based on the results of computational studies. Results further show that ibrutinib and zanubrutinib could exploit different mechanisms at the viral entry and replication stage and could be repurposed as potential inhibitors of SARS-CoV-2 pathogenesis.

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Effects of BTK signalling in pathogenic microorganism infections

Cited by 29 publications

References 65 publications

Relevance of the Bruton Tyrosine Kinase as a Target for COVID-19 Therapy

Relevance of the Bruton Tyrosine Kinase as a Target for COVID-19 Therapy

Bruton tyrosine kinase inhibitors as potential therapeutic agents for COVID-19: A review

Structure-Based Virtual Screening Reveals Ibrutinib and Zanubrutinib as Potential Repurposed Drugs against COVID-19

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