Synthetic Siglec-9 Agonists Inhibit Neutrophil Activation Associated with COVID-19

Delaveris, Corleone; Wilk, Aaron J.; Riley, Nicholas M.; Stark, Jessica C.; Yang, Samuel; Rogers, Angela; Ranganath, Thanmayi; Nadeau, Kari; Blish, Catherine A.; Bertozzi, Carolyn R.

doi:10.26434/chemrxiv.13378148

Cited by 7 publications

(6 citation statements)

References 64 publications

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“…It seemed that pro-inflammatory neutrophil extracellular traps were a critical factor inducing peripheral inflammation and pulmonary tissue damage. They also found Siglec-9 agonist as a therapeutic strategy in controlling neutrophilic hyperinflation in COVID-19 patients because of its ability to suppress NETosis (the cell death pathway associated with the net formation) (9).…”

Section: Key Pointmentioning

confidence: 97%

Treatment of COVID-19 by CD24FC; a mini-review to the current knowledge

Dabaghi¹,

Rad²,

Saberian³

2021

J Prev Epidemiol

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The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is already known for its respiratory infection, but it involved more organs such as the kidney, liver, and heart. Most of the patients with COVID-19 have mild symptoms, but 5% of cases are admitted to an intensive care unit (ICU) for severe symptoms, including multi-organ failure and septic shock. Excessive immune responses play an essential role in sepsis development and are associated with worse prognosis in COVID-19 patients. Consequently, reduction of these immune responses may be helpful for managing COVID-19 patients. In this mini-review, we discuss the prospective role of CD24FC, as a recombinant protein with immunomodulatory function, in the treatment of COVID-19 patients and its mechanism of action in the regulation of the immune system.

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Section: Key Pointmentioning

confidence: 97%

Treatment of COVID-19 by CD24FC; a mini-review to the current knowledge

Dabaghi¹,

Rad²,

Saberian³

2021

J Prev Epidemiol

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“…One of the sialoside analogs shows a potent IC 50 of 0.38 μM against murine and human SIGLEC‐1 and selectively targets SIGLEC‐1 both in vitro and in an animal model 81 . Agonists of Siglec‐9 demonstrated effectiveness against inflammation related to covid, but through a downstream effect 82 . Targeting host lectins by glycomimetics may disrupt their intrinsic biological functions; thus, using these compounds at high concentrations may not be practical for SARS‐CoV‐2 treatment.…”

Section: Glycan‐targeted Therapeutic Candidates For Covid‐19mentioning

confidence: 99%

Involvement of sialoglycans in SARS‐COV‐2 infection: Opportunities and challenges for glyco‐based inhibitors

Kuhaudomlarp

2022

IUBMB Life

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Viral infections have been the causes of global pandemics, including the ongoing coronavirus disease 2019, which prompted the investigation into the infection mechanisms to find treatment and aid the vaccine design. Betacoronaviruses use spike glycoprotein on their surface to bind to host receptors, aiding their host attachment and cell fusion. Protein-glycan interaction has been implicated in the viral entry mechanism of many viruses and has recently been shown in SARS-CoV-2. Here, we reviewed the current knowledge on protein-glycan interactions that facilitate SARS-CoV-2 host entry, with special interest in sialoglycans present on both the virions and host cell surfaces. We also analyze how such information provides opportunities and challenges in glyco-based inhibitors.

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“…The highly sialylated CD24 glycoprotein is able to induce immunosuppression by the ligation of a sialoglycan to sialic acid immunoglobulinlike lectin-10 (Siglec-10), and activates multiple physiological effects, such as mediating a driving force to cancer, damping excessive tissue inflammation, and inducing immune tolerance in pregnancy (134)(135)(136). A novel cell membraneinsertable lipid-modified synthetic sialoglycan has been investigated for immunomodulatory properties (137). It inhibits in vitro overactivation of neutrophils by extracellular neutropil traps (NETosis), in which the biological mechanism is mediated by ITIM-associated SHP-1.…”

Section: Enhancement Of Immunoinhibitory Receptorsmentioning

confidence: 99%

Perspective of Immunopathogenesis and Immunotherapies for Kawasaki Disease

et al. 2021

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Kawasaki Disease (KD) is an acute inflammatory illness that mostly occurs in children below 5 years of age, with intractable fever, mucocutaneous lesions, lymphadenopathy, and lesions of the coronary artery (CAL). KD is sharing clinical symptoms with systemic inflammatory syndrome in children (MIS-C) which is related to COVID-19. Certain genes are identified to be associated with KD, but the findings usually differ between countries and races. Human Leukocyte Antigen (HLA) allele types and toll-like receptor (TLR) expression are also correlated to KD. The acute hyperinflammation in KD is mediated by an imbalance between augmented T helper 17 (Th17)/Th1 responses with high levels of interleukin (IL)-6, IL-10, IL-17A, IFN-γ, and IP-10, in contrast to reduced Th2/Treg responses with lower IL-4, IL-5, FoxP3, and TGF-β expression. KD has varying phenotypic variations regarding age, gender, intravenous immunoglobulin (IVIG) resistance, macrophage activation and shock syndrome. The signs of macrophage activation syndrome (MAS) can be interpreted as hyperferritinemia and thrombocytopenia contradictory to thrombocytosis in typical KD; the signs of KD with shock syndrome (KDSS) can be interpreted as overproduction of nitric oxide (NO) and coagulopathy. For over five decades, IVIG and aspirin are the standard treatment for KD. However, some KD patients are refractory to IVIG required additional medications against inflammation. Further studies are proposed to delineate the immunopathogenesis of IVIG-resistance and KDSS, to identify high risk patients with genetic susceptibility, and to develop an ideal treatment regimen, such as by providing idiotypic immunoglobulins to curb cytokine storms, NO overproduction, and the epigenetic induction of Treg function.

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Synthetic Siglec-9 Agonists Inhibit Neutrophil Activation Associated with COVID-19

Cited by 7 publications

References 64 publications

Treatment of COVID-19 by CD24FC; a mini-review to the current knowledge

Treatment of COVID-19 by CD24FC; a mini-review to the current knowledge

Involvement of sialoglycans in SARS‐COV‐2 infection: Opportunities and challenges for glyco‐based inhibitors

Perspective of Immunopathogenesis and Immunotherapies for Kawasaki Disease

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