Elevated Glucose Levels Favor Sars-Cov-2 Infection and Monocyte Response Through a Hif-1α/Glycolysis Dependent Axis

Codo, Ana Campos; Davanzo, Gustavo Gastão; Monteiro, Lauar de Brito; Souza, Gabriela de Nardi; Muraro, Stéfanie Primon; Carregari, Victor Corasolla; Biagi, Carlos Alberto Oliveira de; Crunfli, Fernanda; Restrepo, Jeffersson Leandro Jimenez; Vendramini, Pedro Henrique; Reis‐de‐Oliveira, Guilherme; Santos, Karina dos; Teixeira, Daniel; Parise, Pierina Lorencini; Martini, Matheus Cavalheiro; Borin, Alexandre; Coimbra, Laís D.; Boldrini, Vinícius O.; Brunetti, Natália S; Vieira, André Schwambach; Mansour, Eli; Spósito, Andrei C.; Carmo, Helison Rafael Pereira do; Ulaf, Raisa G.; Bernardes, Ana Flávia; Nunes, Thyago A.; Palma, André C.; Agrela, Marcus Vinicius Rodrigues de; Moretti, Maria Luíza; Pereira, Fabrício Ramos Silvestre; Velloso, Lı́cio A.; Vinolo, Marco Aurélio Ramirez; Damásio, André; Módena, José Luiz Proença; Carvalho, Robson Francisco; Mori, Marcelo A.; Martins‐de‐Souza, Daniel; Nakaya, Helder I.; Farias, Alessandro Santos; Vieira, Pedro

doi:10.2139/ssrn.3606770

Cited by 146 publications

(187 citation statements)

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“…It is suggested that the pre-existing underlying inflammation in obese patients may result in a dysfunctional immune response during COVID-19, predisposing to a more severe condition ( Seidu et al, 2020 ). Obesity is often associated with type 2 diabetes and it has been shown that uncontrolled glucose levels promote SARS-CoV-2 replication, increase cytokine release and induce T cell dysfunction ( Codo et al, 2020 ; Seidu et al, 2020 ). Hypercoagulopathy, an important component of COVID-19 pathophysiology, is also exacerbated in people with obesity ( Pasquarelli-do-Nascimento et al, 2020 ).…”

Section: Central 5-ht and Its Role In Systemic Inflammationmentioning

confidence: 99%

Can selective serotonin reuptake inhibitors have a neuroprotective effect during COVID-19?

Costa

Santos

Branco

2020

European Journal of Pharmacology

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The absence of a specific treatment for SARS-CoV-2 infection led to an intense global effort in order to find new therapeutic interventions and improve patient outcomes. One important feature of COVID-19 pathophysiology is the activation of immune cells, with consequent massive production and release of inflammatory mediators that may cause impairment of several organ functions, including the brain. In addition to its classical role as a neurotransmitter, serotonin (5-hydroxytryptamine, 5-HT) has immunomodulatory properties, downregulating the inflammatory response by central and peripheral mechanisms. In this review, we describe the roles of 5-HT in the regulation of systemic inflammation and the potential benefits of the use of specific serotonin reuptake inhibitors as a coadjutant therapy to attenuate neurological complications of COVID-19.

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Section: Central 5-ht and Its Role In Systemic Inflammationmentioning

confidence: 99%

Can selective serotonin reuptake inhibitors have a neuroprotective effect during COVID-19?

Costa

Santos

Branco

2020

European Journal of Pharmacology

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“…A meta -analysis of 35 studies revealed that each 1 mmol/L increase in FBG levels augmented the risk of COVID-19 severity by 33% (risk ratio 1.33 [95% CI: 1.26–1.40]). The odds ratio of ICU admission with a FBG of 5.5–6.9 mmol/L was 1.69 and increased to 19.21 when FBG was over 7.0 mmol/L [3] . Furthermore, elevated Hemoglobin A1c levels has been associated with worse COVID-19 prognosis [4] .…”

mentioning

confidence: 91%

“…High levels of fasting blood glucose (FBG) upon hospital admission has been associated with an increased risk for more severe COVID-19 symptoms [2] . Elevated glucose levels has been observed to enhance viral replication trigger increased cytokine production by monocytes in vitro [3] . Here we hypothesize that reduced consumption of added sugars (refined carbohydrates), as well as increased physical activity per capita, could lead to increased individual resistance to COVID-19 pathogenicity.…”

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confidence: 99%

Could diet and exercise reduce risk of COVID-19 syndemic?

2021

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“…Therefore, we should endeavor to search those cells where deamidated HsTIM is accumulating, to study them in light of our proposal. In this regard, some works have recently studied the relationship between glycolysis and SARS-CoV-2 replication, showing that infected monocytes transit to aerobic glycolysis, which facilitates viral replication and the production of soluble mediators that may contribute to lung damage [17]. These monocytes show enhanced glycolysis; then, they might be increasing levels of deamidated HsTIM.…”

Section: Introductionmentioning

confidence: 99%

Deamidated Human Triosephosphate Isomerase is a Promising Druggable Target

et al. 2020

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Therapeutic strategies for the treatment of any severe disease are based on the discovery and validation of druggable targets. The human genome encodes only 600–1500 targets for small-molecule drugs, but posttranslational modifications lead to a considerably larger druggable proteome. The spontaneous conversion of asparagine (Asn) residues to aspartic acid or isoaspartic acid is a frequent modification in proteins as part of the process called deamidation. Triosephosphate isomerase (TIM) is a glycolytic enzyme whose deamidation has been thoroughly studied, but the prospects of exploiting this phenomenon for drug design remain poorly understood. The purpose of this study is to demonstrate the properties of deamidated human TIM (HsTIM) as a selective molecular target. Using in silico prediction, in vitro analyses, and a bacterial model lacking the tim gene, this study analyzed the structural and functional differences between deamidated and nondeamidated HsTIM, which account for the efficacy of this protein as a druggable target. The highly increased permeability and loss of noncovalent interactions of deamidated TIM were found to play a central role in the process of selective enzyme inactivation and methylglyoxal production. This study elucidates the properties of deamidated HsTIM regarding its selective inhibition by thiol-reactive drugs and how these drugs can contribute to the development of cell-specific therapeutic strategies for a variety of diseases, such as COVID-19 and cancer.

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Elevated Glucose Levels Favor Sars-Cov-2 Infection and Monocyte Response Through a Hif-1α/Glycolysis Dependent Axis

Cited by 146 publications

References 0 publications

Can selective serotonin reuptake inhibitors have a neuroprotective effect during COVID-19?

Can selective serotonin reuptake inhibitors have a neuroprotective effect during COVID-19?

Could diet and exercise reduce risk of COVID-19 syndemic?

Deamidated Human Triosephosphate Isomerase is a Promising Druggable Target

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