Exploring the therapeutic potential of forkhead box O for outfoxing COVID-19

Abstract

The COVID-19 pandemic has wreaked unprecedented societal havoc worldwide. The infected individuals may present mild to severe symptoms, with nearly 20% of the confirmed patients impaired with significant complications, including multi-organ failure. Acute respiratory distress imposed by SARS-CoV-2 largely results from an aggravated cytokine storm and deregulated immune response. The forkhead box O (FoxO) transcription factors are reported to play a significant role in maintaining normal cell physiology by regulating survival, apoptosis, oxidative stress, development and maturation of T and B lymphocytes, secretion of inflammatory cytokines, etc. We propose a potent anti-inflammatory approach based on activation of the FoxO as an attractive strategy against the novel coronavirus. This regime will be focused on restoring redox and inflammatory homeostasis along with repair of the damaged tissue, activation of lymphocyte effector and memory cells. Repurposing FoxO activators as a means to alleviate the inflammatory burst following SARS-CoV-2 infection can prove immensely valuable in the ongoing pandemic and provide a reliable groundwork for enriching our repertoire of antiviral modalities for any such complication in the future. Altogether, our review highlights the possible efficacy of FoxO activation as a novel arsenal for clinical management of COVID-19.

An in silico approach towards exploration of the oxidative stress resistance of major withanolides of Withania somnifera in relation to COVID-19 management

“…The diminished anti-oxidant and anti-inflammatory responses in COVID-19 infected patients are the underlying cause for lung injury. The upregulation of FOXO balances the concentration of pro-inflammatory molecules thus aiding repair of the damaged tissues (Cheema et al, 2021).…”

“…The anti-inflammatory potential of FOXO transcription factors along with its role in maintaining normal cell physiology, regulating oxidative stress and immunity has turned the focus of researches for its role in viral infections. FOXO activation is reported to decrease the cytokine storm which is the main cause of mortality in COVID-19 patients and also produce immunological memory (Cheema et al, 2021). The studies on the genes involved in COVID-19 infection and its role in the underlying comorbidities revealed JAK2 as the core hub gene in cardiovascular disease, hypertension as well as kidney disorders (Barh et al, 2021).…”

Neurodegeneration, memory loss, and dementia: the impact of biological clocks and circadian rhythm

“…Mammalian FOXO proteins of the O class are transcription factors and play a significant role in the nervous system. FoxO family members include FOXO1, FOXO3, FOXO4, and FOXO6 [ 67 , 164 , 245 – 247 ] ( Table 1 ). FoxO proteins bind to deoxyribonucleic acid (DNA) through the FoxO-recognized element in the C- terminal basic region of the forkhead DNA binding domain.…”

Potential COVID‐19 therapeutic approaches targeting angiotensin‐converting enzyme 2; An updated review

“…64 Therefore, Antiviral/IFN combination therapy for SARS-CoV-2 infection can assist in balancing host restriction, tissue tolerance, and viral enhancement mechanisms. [65][66][67] SARS coronavirus infection correlates with cell differentiation of airway epithelia and ACE2 expression and localization. 68,69 ACE2 proteins are more abundantly expressed on the apical than the basolateral surface of polarized airway epithelia.…”

“…SARS‐CoV‐2 may increase infection via interferon (IFN)‐driven upregulation of ACE2, a key tissue‐protective mediator during lung injury 64 . Therefore, Antiviral/IFN combination therapy for SARS‐CoV‐2 infection can assist in balancing host restriction, tissue tolerance, and viral enhancement mechanisms 65–67 …”