The influence of pH on SARS-CoV-2 infection and COVID-19 severity

Jimenez, Leandro; Codo, Ana Campos; Sampaio, Vanderson Souza; Oliveira, Antônio Edson Rocha; Ferreira, Lucas Kk; Davanzo, Gustavo Gastão; Monteiro, Lauar de Brito; Virgílio-da-Silva, João Victor; Borba, Mayla Gs; Souza, Gabriela Fabiano de; Zini, Nathalia; Gandolfi, Flora A; Murano, Stefanie P; Proença-Módena, José Luiz; Val, Fernando Almeida; Melo, Gisely Cardoso de; Nogueira, Maurício Lacerda; Lacerda, Marcus; Moraes‐Vieira, Pedro M.; Nakaya, Helder I.

doi:10.1101/2020.09.10.20179135

Cited by 8 publications

(6 citation statements)

References 30 publications

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“…Briefly, SARS-CoV-2 can induce anaerobic metabolism via the disruption of cell oxygenation and the induction of anaerobic glycolysis (95). As cell pH is controlled by Na + /H + and lactate/H + exchangers and symporters, respectively, high lactate serum levels in SARS-CoV-2 raise the activity of the lactate/H + symporter with subsequent cell acidosis (96). Dapagliflozin inhibits cell Na + /H + exchangers, thus reducing cell acidosis and SARS-CoV-2 activation at acidic pH.…”

Section: Sodium-glucose Co-transporter-2 Inhibitorsmentioning

confidence: 99%

COVID-19 in Relation to Hyperglycemia and Diabetes Mellitus

Al-Kuraishy¹,

Al-Gareeb²,

Alblihed

et al. 2021

Front. Cardiovasc. Med.

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Coronavirus disease 2019 (COVID-19), triggered by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), may lead to extrapulmonary manifestations like diabetes mellitus (DM) and hyperglycemia, both predicting a poor prognosis and an increased risk of death. SARS-CoV-2 infects the pancreas through angiotensin-converting enzyme 2 (ACE2), where it is highly expressed compared to other organs, leading to pancreatic damage with subsequent impairment of insulin secretion and development of hyperglycemia even in non-DM patients. Thus, this review aims to provide an overview of the potential link between COVID-19 and hyperglycemia as a risk factor for DM development in relation to DM pharmacotherapy. For that, a systematic search was done in the database of MEDLINE through Scopus, Web of Science, PubMed, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), and Wanfang Data. Data obtained underline that SARS-CoV-2 infection in DM patients is more severe and associated with poor clinical outcomes due to preexistence of comorbidities and inflammation disorders. SARS-CoV-2 infection impairs glucose homeostasis and metabolism in DM and non-DM patients due to cytokine storm (CS) development, downregulation of ACE2, and direct injury of pancreatic β-cells. Therefore, the potent anti-inflammatory effect of diabetic pharmacotherapies such as metformin, pioglitazone, sodium-glucose co-transporter-2 inhibitors (SGLT2Is), and dipeptidyl peptidase-4 (DPP4) inhibitors may mitigate COVID-19 severity. In addition, some antidiabetic agents and also insulin may reduce SARS-CoV-2 infectivity and severity through the modulation of the ACE2 receptor expression. The findings presented here illustrate that insulin therapy might seem as more appropriate than other anti-DM pharmacotherapies in the management of COVID-19 patients with DM due to low risk of uncontrolled hyperglycemia and diabetic ketoacidosis (DKA). From these findings, we could not give the final conclusion about the efficacy of diabetic pharmacotherapy in COVID-19; thus, clinical trial and prospective studies are warranted to confirm this finding and concern.

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Section: Sodium-glucose Co-transporter-2 Inhibitorsmentioning

confidence: 99%

COVID-19 in Relation to Hyperglycemia and Diabetes Mellitus

Al-Kuraishy¹,

Al-Gareeb²,

Alblihed

et al. 2021

Front. Cardiovasc. Med.

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“…Analysis of seven studies (9-15) on risk of COVID-19 infection found that the use of The result of nine studies from eight original articles (7,9,(16)(17)(18)(19)(20)(21) showed that PPI use was associated with increased risk of severe disease, including admission to ICU, intubation, and death, for COVID-19 patients (OR=1.67, 95% CI=1.37-2.02, P<0.001; I 2 =67%, Pheterogeneity=0.002) (Figure 3). In subgroup analysis by study designs, a nonsignificant increased risk was observed in cohort studies (OR:1.39, 95%CI = 0.96-2.01, P=0.080; I 2 =65%, Pheterogeneity =0.060), and a statistically significant increased risk was found for case-control studies (OR:1.86, 95%CI = 1.46-2.37, P=0.410; I 2 =56%, Pheterogeneity =0.040).…”

Section: Association Between Ppi Use and Risk Of Covid-19 Infectionmentioning

confidence: 99%

Does Proton Pump Inhibitor Use Lead to a Higher Risk of Coronavirus Disease 2019 Infection and Progression to Severe Disease? a Meta-analysis

et al. 2022

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Previous researches on the association between proton pump inhibitors (PPIs) use and the treatment and prevention of COVID-19 has generated inconsistent findings.Therefore, this meta-analysis was conducted to clarify the outcome in patients who take PPIs.Eight articles with more than 268,683 subjects were included. PPI use was not associated with increased or decreased risk of COVID-19 infection (OR:3.16, 95%CI = 0.74-13.43, P=0.12) or mortality risk of COVID-19 patients (OR=1.91, 95% CI=0.86-4.24, P=0.11). While it can add risk of severe disease (OR=1.54, 95% CI=1.20-1.99, P<0.001;) and secondary infection (OR=4.33, 95% CI=2.57-7.29).In summary, PPI use is not associated with an increased risk of infection and may not change the mortality risk of COVID-19, but appeared to be associated with an increased risk of progression to severe disease and secondary infection. However, more original studies to further clarify the relationship between PPI and COVID-19 are still urgently needed.

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“…The S protein conformational heterogeneity to be reduced between pH5.5 and pH4.5, and then to remain unchanged as pH was reduced further (from pH4.5 to pH4) [21]. On the other hand, weak acid pH (pH6-6.5) increases SARS-CoV-2 viral load and infection with increased expression of ACE2 [35]. These data imply that, in weak acid, the S protein is more likely to bind with ACE2, which is consistent with our results (the RBD mass deviation of pH5 is slightly higher than that of pH7).…”

Section: Corroborations With In Vitro Experimentsmentioning

confidence: 99%

Molecular Dynamics Modeling of the SARS-CoV-2 Spike Protein at PH2 Through PH11.5

Niu

Zhang

Rafailovich

et al. 2021

Preprint

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The spike glycoprotein (S protein) of the SARS-CoV-2 that has be studied extensively in vitro is modeled by all-atom molecular dynamics for its conformational states at six pH values ranging from 2 to 11.5. The MD simulations up to 3.7 T demonstrate interesting discoveries while confirming known facts. (1). At pH2, the protein’s time averaged RMSD is 62.5% higher than that of pH7, as the control group, and the receptor binding domain (RBD) deviates from that of pH7 by 200%. (2). For pH4 through pH10.5, the S protein remains relatively stable evident by the invariance of the side chain H bond counts and RMSD from pH7, suggesting high tolerance of the S protein to a wide range of pH values other than the extreme acidic and basic conditions. (3). For pH2 to pH4, the structure of the S protein alters significantly, suggesting the existence of a critical pH value at which the S protein responds to acid sharply. (4). In the residue-based relative entropy analysis, we identify several RBM and RBD residue clusters with maximum deviations that cause the overall protein structure changes.

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The influence of pH on SARS-CoV-2 infection and COVID-19 severity

Cited by 8 publications

References 30 publications

COVID-19 in Relation to Hyperglycemia and Diabetes Mellitus

COVID-19 in Relation to Hyperglycemia and Diabetes Mellitus

Does Proton Pump Inhibitor Use Lead to a Higher Risk of Coronavirus Disease 2019 Infection and Progression to Severe Disease? a Meta-analysis

Molecular Dynamics Modeling of the SARS-CoV-2 Spike Protein at PH2 Through PH11.5

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