An Oral Galectin Inhibitor in COVID-19—A Phase II Randomized Controlled Trial

Sigamani, Alben; Mayo, Kevin H.; Miller, Michelle C.; Chen-Walden, Hana; Reddy, Surendar; Platt, David

doi:10.3390/vaccines11040731

Cited by 8 publications

(6 citation statements)

References 42 publications

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“…This review proposed the idea of using Gal-3 antagonists given the structural similarity, which is remarkably studied to have benefits to clinical prognostication. Prolectin-M, a gal-3 antagonist, was studied for the treatment of SARS-CoV-2 infection (Galectin Antagonist Use in Mild Cases of SARS-CoV-2; pilot feasibility randomized, open label, controlled trial [109]). inhibitor, GB0139, when compared to standard treatment [86].…”

Section: Galectin Inhibitors In Pulmonary Fibrosis and Covid-19 Respi...mentioning

confidence: 99%

Galectin inhibitors and nanoparticles as a novel therapeutic strategy for glioblastoma multiforme

Elliott Jr

2024

Am J Cancer Res

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Over the past two decades, the gold standard of glioblastoma multiforme (GBM) treatment is unchanged and adjunctive therapy has offered little to prolong both quality and quantity of life. To improve pharmacotherapy for GBM, galectins are being studied provided their positive correlation with the malignancy and disease severity. Despite the use of galectin inhibitors and literature displaying the ability of the lectin proteins to decrease tumor burden and decrease mortality within various malignancies, galectin inhibitors have not been studied for GBM therapy. Interestingly, anti-galectin siRNA delivered in nanoparticle capsules, assisting in blood brain barrier penetrance, is well studied for GBM, and has demonstrated a remarkable ability to attenuate both galectin and tumor count. Provided that the two therapies have an analogous anti-galectin effect, it is hypothesized that galectin inhibitors encapsuled within nanoparticles will likely have a similar anti-galectin effect in GBM cells and further correlate to a repressed tumor burden.

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Section: Galectin Inhibitors In Pulmonary Fibrosis and Covid-19 Respi...mentioning

confidence: 99%

Galectin inhibitors and nanoparticles as a novel therapeutic strategy for glioblastoma multiforme

Elliott Jr

2024

Am J Cancer Res

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“…Galectin-3 may play a role in sustaining HBV replication through stimulating the production of cytokines and chemokines via Cluster of Differentiation 98 (CD98) interactions with macrophages [23]. In the context of SARS-CoV-2, Gal-3 inhibition could potentially influence viral RNA synthesis [24].…”

Section: Galectin-3 In Viral Replicationmentioning

confidence: 99%

“…Small molecule inhibitors targeting Gal-3 have shown potential as antiviral agents in preclinical studies, reducing viral replication and alleviating virus-induced inflammation [24]. The Gal-3 inhibitor TD139 has demonstrated significant reductions in lung fibrosis and ß-catenin activation in animal models of pulmonary fibrosis and is now in phase IIb trials for the treatment of idiopathic pulmonary fibrosis and COVID-19 [109].…”

Section: Small Molecule Inhibitors Of Galectin-3mentioning

confidence: 99%

The Pivotal Role of Galectin-3 in Viral Infection: A Multifaceted Player in Host–Pathogen Interactions

Stojanović

Milovanović

et al. 2023

IJMS

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Galectin-3 (Gal-3), a beta-galactoside-binding lectin, plays a pivotal role in various cellular processes, including immune responses, inflammation, and cancer progression. This comprehensive review aims to elucidate the multifaceted functions of Gal-3, starting with its crucial involvement in viral entry through facilitating viral attachment and catalyzing internalization. Furthermore, Gal-3 assumes significant roles in modulating immune responses, encompassing the activation and recruitment of immune cells, regulation of immune signaling pathways, and orchestration of cellular processes such as apoptosis and autophagy. The impact of Gal-3 extends to the viral life cycle, encompassing critical phases such as replication, assembly, and release. Notably, Gal-3 also contributes to viral pathogenesis, demonstrating involvement in tissue damage, inflammation, and viral persistence and latency elements. A detailed examination of specific viral diseases, including SARS-CoV-2, HIV, and influenza A, underscores the intricate role of Gal-3 in modulating immune responses and facilitating viral adherence and entry. Moreover, the potential of Gal-3 as a biomarker for disease severity, particularly in COVID-19, is considered. Gaining further insight into the mechanisms and roles of Gal-3 in these infections could pave the way for the development of innovative treatment and prevention options for a wide range of viral diseases.

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“…In the case of SARS-CoV-2, it has been shown that lectin receptors such as DC-SIGN, L-SIGN, CLEC4G and SIGLEC can bind to the glycans on the surface of the S protein and “hold” the virus in close proximity to cells, thereby facilitating more efficient infection [ 41 , 42 , 43 , 44 , 45 ]. There is also evidence that soluble lectin proteins—such as galectins—can bind to virions and bring them in close proximity to host cells, also facilitating infection [ 46 , 47 , 48 ]. This is particularly pertinent for the progression of COVID-19 since SARS-CoV-2 virions are transmitted via airborne routes and infection initiates in the proximal airways [ 42 , 49 ].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Select SARS-CoV-2 N-Linked Glycan and Variant of Concern Spike Protein Mutations on C-Type Lectin-Receptor-Mediated Infection

Bains,

Guan,

LiWang

2023

Viruses

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The SARS-CoV-2 virion has shown remarkable resilience, capable of mutating to escape immune detection and re-establishing infectious capabilities despite new vaccine rollouts. Therefore, there is a critical need to identify relatively immutable epitopes on the SARS-CoV-2 virion that are resistant to future mutations the virus may accumulate. While hACE2 has been identified as the receptor that mediates SARS-CoV-2 susceptibility, it is only modestly expressed in lung tissue. C-type lectin receptors like DC-SIGN can act as attachment sites to enhance SARS-CoV-2 infection of cells with moderate or low hACE2 expression. We developed an easy-to-implement assay system that allows for the testing of SARS-CoV-2 trans-infection. Using our assay, we assessed how SARS-CoV-2 Spike S1-domain glycans and spike proteins from different strains affected the ability of pseudotyped lentivirions to undergo DC-SIGN-mediated trans-infection. Through our experiments with seven glycan point mutants, two glycan cluster mutants and four strains of SARS-CoV-2 spike, we found that glycans N17 and N122 appear to have significant roles in maintaining COVID-19′s infectious capabilities. We further found that the virus cannot retain infectivity upon the loss of multiple glycosylation sites, and that Omicron BA.2 pseudovirions may have an increased ability to bind to other non-lectin receptor proteins on the surface of cells. Taken together, our work opens the door to the development of new therapeutics that can target overlooked epitopes of the SARS-CoV-2 virion to prevent C-type lectin-receptor-mediated trans-infection in lung tissue.

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An Oral Galectin Inhibitor in COVID-19—A Phase II Randomized Controlled Trial

Cited by 8 publications

References 42 publications

Galectin inhibitors and nanoparticles as a novel therapeutic strategy for glioblastoma multiforme

Galectin inhibitors and nanoparticles as a novel therapeutic strategy for glioblastoma multiforme

The Pivotal Role of Galectin-3 in Viral Infection: A Multifaceted Player in Host–Pathogen Interactions

The Effect of Select SARS-CoV-2 N-Linked Glycan and Variant of Concern Spike Protein Mutations on C-Type Lectin-Receptor-Mediated Infection

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