Is sitagliptin effective for SARS-CoV-2 infection: false or true prophecy?

Abstract

Coronavirus disease 2019 (Covid-19) is caused by severe acute respiratory syndrome type 2 (SARS-CoV-2). Covid-19 is characterized by hyperinflammation, oxidative stress, and multi-organ injury (MOI) such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Covid-19 is mainly presented with respiratory manifestations; however, extra-pulmonary manifestations may also occur. Extra-pulmonary manifestations of Covid-19 are numerous including: neurological, cardiovascular, renal, endocrine, and hematological complications. Notably, a cluster of differentiation 26 (CD26) or dipeptidyl peptidase-4 (DPP-4) emerged as a new receptor for entry of SARS-CoV-2. Therefore, DPP-4 inhibitors like sitagliptin could be effective in treating Covid-19. Hence, we aimed in the present critical review to assess the potential role of sitagliptin in Covid-19. DPP-4 inhibitors are effective against the increased severity of SARS-CoV-2 infections. Moreover, DPP-4 inhibitors inhibit the interaction between DPP-4 and scaffolding proteins which are essential for endosome formation and replication of SARS-CoV-2. Therefore, sitagliptin through attenuation of the inflammatory signaling pathway and augmentation of stromal-derived factor-1 (SDF-1) may decrease the pathogenesis of SARS-CoV-2 infection and could be a possible therapeutic modality in treating Covid-19 patients. In conclusion, the DPP-4 receptor is regarded as a potential receptor for the binding and entry of SARS-CoV-2. Inhibition of these receptors by the DPP-4 inhibitor, sitagliptin, can reduce the pathogenesis of the infection caused by SARS-CoV-2 and their associated activation of the inflammatory signaling pathways.

SIRT1 pathway in Parkinson’s disease: a faraway snapshot but so close

“…It was (Nadwa et al 2022 ) demonstrated that SIRT1 activation by resveratrol was mediated and dependent on the activity of lamin A protein. Dysregulation of lamin A protein attenuates PGC1-α/NAD with subsequent reduction of SIRT1 activity and development of mitochondrial dysfunction (Alomair et al 2022 ). These verdicts indicated that lamin A protein plays a crucial role in SIRT1 expression and activation.…”

“…Lamin protein is the only nuclear protein expressed in the CNS, essential for neuronal differentiation and survival. Lamin A protein is critical for lifespan through inhibition of neurodegeneration (Alomair et al 2022 ). It has been reported that mutation with reduced expression of lamin A protein was linked with the development of aging-related degenerative brain disease including PD.…”

Effect of DPP4/CD26 expression on SARS‑CoV‑2 susceptibility, immune response, adenosine (derivatives m62A and CD) regulations on patients with cancer and healthy individuals

“…The levels of soluble DPP4 (sDPP4) levels were increased in patients with acute and chronic viral infections; thus, the concentration of sDPP4 might be useful as a biomarker for these diseases ( 74 ). DPP4 inhibitors (e.g., gliptins) could be beneficial for patients with COVID-19, probably through interference with viral invasion ( 74 ) and activation of inflammatory pathways ( 75 ).…”

Association of hypernatremia with mortality in patients with COVID‐19: A systematic review and meta‐analysis

“…COVID‐19 pandemics around the world are primarily caused by SARS‐CoV‐2 infections, and the clinical presentation can range from asymptomatic to mild upper respiratory tract infections or severe lung injury. SARS‐CoV‐2 infection induces a cytokine storm (CS) leading to the release of proinflammatory cytokines, such as interleukin (IL)−6, IL‐1β, and tumor necrosis factor (TNF)‐α, which play an important role in the progression of COVID‐19, and the mechanism is mainly related to the interaction between SARS‐CoV‐2 and immune cells 26,27 . According to research, COVID‐19 severity and clinical prognosis are strongly linked to CS 28 …”