PI3Kδ Inhibition as a Potential Therapeutic Target in COVID-19

Abstract

The spread of the novel human respiratory coronavirus (SARS-CoV-2) is a global public health emergency. There is no known successful treatment as of this time, and there is a need for medical options to mitigate this current epidemic. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor and is primarily trophic for the lower and upper respiratory tract. A number of current studies on COVID-19 have demonstrated the substantial increase in pro-inflammatory factors in the lungs during infection. The virus is also documented in the central nervous system and, particularly in the brainstem, which plays a key role in respiratory and cardiovascular function. Currently, there are few antiviral approaches, and several alternative drugs are under investigation. Two of these are Idelalisib and Ebastine, already proposed as preventive strategies in airways and allergic diseases. The interesting and evolving potential of phosphoinositide 3-kinase δ (PI3Kδ) inhibitors, together with Ebastine, lies in their ability to suppress the release of pro-inflammatory cytokines, such as IL-1β, IL-8, IL-6, and TNF-α, by T cells. This may represent an optional therapeutic choice for COVID-19 to reduce inflammatory reactions and mortality, enabling patients to recover faster. This concise communication aims to provide new potential therapeutic targets capable of mitigating and alleviating SARS-CoV-2 pandemic infection.

Allergic Reactions to Current Available COVID-19 Vaccinations: Pathophysiology, Causality, and Therapeutic Considerations

“…Immunoglobulin E antibodies are synthesized and released by B lymphocytes as a result of a complex interplay between genes, cytokines, and environmental antigen exposure. They constitute components of a protein network implicated in signaling response to antigens/allergens, and participate in atopic diseases and systemic anaphylaxis [ 65 ]. Additionally, IgEs might be increased in acute myocardial infarction, stable and unstable angina, further correlating with plaque destabilization and severity of acute myocardial infarction [ 66 ], while elevated IgE levels may be a risk factor for increased cardiovascular mortality [ 67 ].…”

Skin Manifestation of SARS-CoV-2: The Italian Experience

“…The situation is still changing rapidly [ 56 , 57 , 58 , 59 , 60 ] but a growing knowledge of the etiopathogenetic mechanisms potentially responsible for these skin manifestations is gradually emerging. Below, we summarize the clinical and histopathologic characteristics described to date.…”

COVID-19 and Pregnancy: Vertical Transmission and Inflammation Impact on Newborns

“…Perinatal inflammation during the developmental phase can affect the brain during the fetal period as well as over a long period in postnatal life, where it can affect cortical plasticity and myelination, thus producing an adverse effect on neural connections and the rate of neural message delivery [ 105 ]. Phosphoinositide 3-kinase δ (PI3Kδ) inhibitors which are used as a therapeutic target for the inhibition of proinflammatory cytokines can be used to suppress a cytokine storm, and consequently might stop the drastic negative effect that inflammation can cause on neonatal brain development [ 106 ].…”