Metformin Regulates the Inflammatory Response of Human Monocytes to SARS-CoV-2 Spike Glycoprotein
Abstract
Background: A hyperinflammatory state is associated with coronavirus disease 2019 (COVID-19) severity and mortality. This inflammatory process begins when severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the hosts respiratory epithelium using the spike glycoprotein (S protein) to bind to the hosts cellular angiotensin-converting enzyme 2 receptor. Downstream proinflammatory response of immune cells eventually results in production of excessive pro-inflammatory cytokines in some individuals. Metformin (MTF) has been proposed as an adjunctive therapy for COVID-19 due to its antiviral and anti-inflammatory properties.
Methods: In our study, we compared the inflammatory response of monocytes to various SARS-CoV-2 S proteins in cells treated with MTF.
Results: We observed a differential interferon regulatory factor (IRF) and nuclear factor kappa B activation by SARS-CoV-2 S proteins in human monocytes, and a decreased IRF activation, although this was not statistically significant. MTF treatment reduced type I interferon (IFN) transcription upon human monocytes stimulation with a stabilized trimeric S protein.
Conclusion: As type I IFNs can regulate the expression of other cytokines, MTF treatment may offer protection to severe COVID-19, and help reduce disease severity and mortality.
Clin Infect Immun. 2021;6(3):82-85
doi: https://doi.org/10.14740/cii137