Investigation of the Therapeutic Effect of Remdesivir on Rapoport Shunt and Oxygen Delivery in Patients with COVID-19

Background: The respiratory effects of SARS-CoV-2, along with resultant hypoxia, pose a significant threat to human health, often culminating in fatalities. In response to this challenge, the human body activates various defense mechanisms, including the Rapoport-Luebering shunt within the glycolysis pathway. This pathway facilitates the production of 2,3-bisphosphoglycerate (2,3-BPG) through specific enzymes, enhancing oxygen delivery to tissues. Objectives: This study investigates the effects of remdesivir (REM) on the Rapoport-Luebering shunt in COVID-19 patients by analyzing its impact on phosphoglycerate mutase (PGM) and phosphoglycerate phosphatase (PGP) expression to improve oxygen delivery and reduce hypoxia. Methods: Participants were randomly selected and categorized into three groups: Healthy individuals, mild outpatient cases, and severe hospitalized patients. The severe patient cohort was further divided into two subgroups based on REM administration. mRNA extraction followed by cDNA synthesis using real-time PCR enabled the quantification of PGM and PGP expression levels, key enzymes of the Rapoport-Luebering shunt. Results: The analysis revealed increased PGM gene expression and decreased PGP gene expression in COVID-19 patients compared to healthy controls. These variations were consistent across study cohorts, suggesting correlations with disease severity and REM treatment. Conclusions: The upregulation of 2,3-BPG synthesis, attributed to elevated PGM expression and diminished PGP expression in SARS-CoV-2-infected individuals, serves as a compensatory mechanism to alleviate coronavirus-induced hypoxia. Interventions targeting the modulation of these genes hold promise in mitigating hypoxia-related mortality among hospitalized COVID-19 patients. Further exploration of pharmacological agents capable of enhancing PGM expression and inhibiting PGP expression is warranted to optimize therapeutic strategies targeting COVID-19-associated hypoxia.