Dipyridamole and adenosinergic pathway in Covid-19: a juice or holy grail

Abstract

Background Coronavirus disease 2019 (Covid-19) is an infectious worldwide pandemic triggered by severe acute respiratory coronavirus 2 (SARS-CoV-2). This pandemic disease can lead to pro-inflammatory activation with associated acute lung injury and acute respiratory distress syndrome. Main body of the abstract SARS-CoV-2 infection is linked with inhibition of adenosine and activation of phosphodiesterase. Dipyridamole (DIP) is a nucleoside transport and phosphodiesterase inhibitor so that it may potentially affect SARS-CoV-2 infection and its accompanying inflammations. Therefore, the primary objective of this mini-review study was to elucidate the potential beneficial impacts of DIP on the adenosinergic pathway in Covid-19. A systemic search was done using online databases with relevant keywords. The findings of the present study illustrated that DIP directly or indirectly, through augmentation of adenosine and inhibition of phosphodiesterase, mitigates Covid-19 outcomes. Conclusion Our study concluded that DIP has a potential therapeutic effect in the management and treatment of Covid-19. This could be attained either directly, through anti-SARS-CoV-2, anti-inflammatory, and anti-platelets properties, or indirectly, through augmentation of extracellular adenosine, which has anti-inflammatory and immune-regulatory effects. However, extensive randomized clinical trials, and clinical and prospective research in this area are required to demonstrate the safety and therapeutic efficacy of DIP and adenosine modulators in the treatment of Covid-19.

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

“…SRT-1720 increases the lifespan of obese mice by improving SIRT1 activity. SRT-1720 is not under clinical improvement through a related compound SRT-2104 pass Phase I clinical trial for the management of metabolic disorders (Al-kuraishy et al 2022 ; Dai et al 2010 ). In vitro study observed that SRT-1720 was not toxic to cell lines.…”

Receptor-dependent effects of sphingosine-1-phosphate (S1P) in COVID-19: the black side of the moon

“…In their research, Michaud et al observed that S1P is regarded as a novel non-hypoxic stimulus that induces hypoxia-inducible factor (HIF-1) [ 47 ]. It has been proposed that high HIF-1 may protect against COVID-19 severity by decreasing ferritin and modulating ACE2 expression [ 48 , 49 ]. Hence, the protective role of S1P in COVID-19 is exerted through S1PR1 binding and responsive downstream effect.…”

Dantrolene and ryanodine receptors in COVID‐19: The daunting task and neglected warden

“…In COVID‐19, oxidative stress is augmented because of the generation of ROS and a reduction in antioxidant capacity, causing widespread tissue damage 92–94 . DTN has been demonstrated to protect against oxidative stress by inhibiting RyRs‐dependent production of reactive oxygen species (ROS) with increasing activity of antioxidant enzymes 95 .…”

“…In COVID-19, oxidative stress is augmented because of the generation of ROS and a reduction in antioxidant capacity, causing widespread tissue damage. [92][93][94] DTN has been demonstrated to protect against oxidative stress by inhibiting RyRs-dependent production of reactive oxygen species (ROS) with increasing activity of antioxidant enzymes. 95 Moreover, mitochondrial Ca 2+ overload triggers production of ROS, which stimulates activation of RyRs, causing autophagy, apoptosis and impairment of ATP production with the development of mitochondrial dysfunction.…”