BTK/ITK dual inhibitors: Modulating immunopathology and lymphopenia for COVID-19 therapy

McGee, Michael C; August, Avery; Huang, Weishan

doi:10.1002/jlb.5covr0620-306r

Cited by 29 publications

(20 citation statements)

References 33 publications

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“…The hence might be beneficial in treating COVID-19 related immunopathology and lymphopenia 53 . This has been already tested in clinical trials 54 and for dasatinib it has been confirmed from seminal studies in chronic myelogenous leukemia 55 inhibition of the viral replication mechanisms and c) where required, protective effects which account for other underlying conditions like cardiovascular disease.…”

Section: Discussionmentioning

confidence: 99%

Multi-omics data integration and network-based analysis drives a multiplex drug repurposing approach to a shortlist of candidate drugs against COVID-19

Tomazou

Bourdakou

Minadakis

et al. 2020

Preprint

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The SARS-CoV-2 pandemic is undeniably the most severe global health emergency since the 1918 Influenza outbreak. Depending on its evolutionary trajectory, the virus is expected to establish itself as an endemic infectious respiratory disease exhibiting seasonal flare-ups. Therefore, despite the unprecedented rally to reach a vaccine that can offer widespread immunization, it is equally important to reach effective prevention and treatment regimens for COVID-19. Contributing to this effort, we have curated and analyzed multi-source and multi-omics publicly available data from patients, cell lines and databases in order to fuel a multiplex computational drug repurposing approach. We devised a Network-based integration of multi-omic data to prioritize the most important genes related to COVID-19 and subsequently rerank the identified candidate drugs. We concluded to a highly informed integrated drug shortlist by combining structural diversity filtering along with experts’ curation and drug-target mapping on the depicted molecular pathways. In addition to the recently proposed drugs that are already generating promising results such as dexamethasone and remdesivir, our list includes inhibitors of Src Tyrosine Kinase (bosutinib, dasatinib, cytarabine and saracatinib) which appear to be involved in multiple COVID-19 pathophysiological mechanisms. In addition, we highlight specific immunomodulators and anti-inflamatory drugs like dactolisib and methotrexate and inhibitors of histone deacetylase like hydroquinone and vorinostat with potential beneficial effects in their mechanisms of action.

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Section: Discussionmentioning

confidence: 99%

Multi-omics data integration and network-based analysis drives a multiplex drug repurposing approach to a shortlist of candidate drugs against COVID-19

Tomazou

Bourdakou

Minadakis

et al. 2020

Preprint

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show abstract

“…Therefore, NF-kB plays a key role in the pathogenesis of coronaviruses ( DeDiego et al, 2014 ; Kanzawa et al, 2006 ; Yang et al, 2017 ). It has been observed that tyrosine kinase activity is increased in COVID-19 ( McGee et al, 2020 ), which leads to phospholipase C (PLC) activation that actives protein kinase C (PKC). This induces reactive oxygen species (ROS) increase, ROS-mediated NF-kappa B (NF-kB) activation, and mTOR inhibition, which result in the transcriptional activation of NF-kB target genes.…”

Section: Mainmentioning

confidence: 99%

Protection against COVID-19 in African population: Immunology, genetics, and malaria clues for therapeutic targets

Altable¹,

Serna

2021

Virus Research

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Background There is a marked discrepancy between SARS-CoV-2 seroprevalence and COVID-19 cases and deaths in Africa. Main SARS-CoV-2 stimulates humoral and cellular immunity systems, as well as mitogen-activated protein kinase (MAPK) and nuclear NF-kB signalling pathways, which regulate inflammatory gene expression and immune cell differentiation. The result is pro-inflammatory cytokines release, hyperinflammatory condition, and cytokine storm, which provoke severe lung alterations that can lead to multi-organ failure in COVID-19. Multiple genetic and immunologic factors may contribute to the severity of COVID-19 in African individuals when compared to the rest of the global population. In this article, the role of malaria, NF-kB and MAPK pathways, caspase-12 expression, high level of LAIR-1-containing antibodies, and differential glycophorins (GYPA/B) expression in COVID-19 are discussed. Conclusion Understanding pathophysiological mechanisms can help identify target points for drugs and vaccines development against COVID-19. To our knowledge, this is the first study that explores this link and proposes a biological and molecular answer to the epidemiologic discrepancy in COVID-19 in Africa.

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“…These patients display lymphopenia, stimulation and malfunction of lymphocytes, defects of granulocytes and monocytes, elevated levels of cytokines, and higher amounts of immunoglobulin G (IgG) and total antibodies [66] (Figure 8). Extreme and fatal COVID-19 is linked with lymphopenia and an elevated amount of blood neutrophils [67]. Lymphocyte counts of 800 cells/μl and a decreased probability of recovery are reported in ICU patients suffering from COVID-19.…”

Section: Immunopathology Of Sars-cov2mentioning

confidence: 99%

SARS-CoV-2 and Coronavirus Ancestors under a Molecular Scope

Abdelghany¹,

Alghamdi²,

Eid³

2021

Cell Interaction - Molecular and Immunological Basis for Disease Management

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The Pandemic of COVID-19 has been thoroughly followed and discussed on many levels due to the high level of attention that it has brought by its effect on the world. While this disease might seem like to arise out of the blue, we will shed light on COVID-19 disease which is caused by the virus SARS-CoV2 and belong to family of coronaviruses. We will discuss current knowledge about SARS-CoV2 emergence, diagnosis, its mode of action, and genomic information, For an antiviral treatment to be used, it should be preceded by a foundation of information about the virus genome and its family as discussed in this review.

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BTK/ITK dual inhibitors: Modulating immunopathology and lymphopenia for COVID-19 therapy

Cited by 29 publications

References 33 publications

Multi-omics data integration and network-based analysis drives a multiplex drug repurposing approach to a shortlist of candidate drugs against COVID-19

Multi-omics data integration and network-based analysis drives a multiplex drug repurposing approach to a shortlist of candidate drugs against COVID-19

Protection against COVID-19 in African population: Immunology, genetics, and malaria clues for therapeutic targets

SARS-CoV-2 and Coronavirus Ancestors under a Molecular Scope

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