(W0930-04-20) Kruppel-Like Factor 2 (KLF2) Reduces Parameters of Coronavirus Disease-Related Pathogenesis

Purpose: The goal of this study is to investigate how Kruppel-like factor 2 (KLF2) plays a role in mitigating COVID-19-related pathogenesis and identify it as a potential therapeutic target for COVID-19.

Methods: Lymphoid cells were transfected with COVID-19( N and S) proteins to simulate COVID-19 infection. Changes in inflammation, oxidative stress, and mitochondrial function were assessed in transfected cells. Treatment with GGTI298, a chemical inducer of KLF2, was administered to evaluate its effects on cytokine storm attenuation and mitochondrial function restoration. An induced lung fibrosis model was utilized to examine the impact of KLF2 induction on fibrosis-associated markers in lung fibroblast cells. Statistical analyses, such as correlation studies and differential gene expression analysis, are performed to assess the association between genetic profiles and COVID-19 susceptibility, severity, or outcomes.

Results: Transfected lymphoid cells exhibited heightened inflammation and decreased KLF2 expression, accompanied by elevated oxidative stress and mitochondrial dysfunction. Treatment with GGTI298 attenuated the cytokine storm and restored mitochondrial function by reducing oxidative stress. Induction of KLF2 in the induced lung fibrosis model resulted in reduced fibrosis-associated markers in lung fibroblast cells. Patterns of genetic variation associated with COVID-19 susceptibility, severity, or outcomes are elucidated, contributing to our understanding of the molecular mechanisms underlying COVID-19 pathogenesis.

Conclusion: KLF2 emerges as a promising therapeutic target for COVID-19, with potential applications in attenuating inflammation, restoring mitochondrial function, and reducing fibrosis-associated markers. These findings shed light on the molecular mechanisms underlying COVID-19 pathogenesis and pave the way for the development of targeted treatments to address this global health crisis.

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Acknowledgements: NIH

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