Christine Wilson
It is essential to identify the signalling pathways and molecules involved in SARS-CoV-2 pathogenesis in order to create novel, potent therapeutic or preventive COVID-19 treatments. The Plasma Membrane's Pannexins (PANX) are ATP-release channels that are crucial for various physiological and immunological responses. In viral infection, activation of pannexin channels and downstream purinergic receptors can either promote viral replication and infection or trigger host antiviral response. The current review presents a theory illustrating the potential involvement of purinergic receptors and the PANX1 channel in the pathophysiology and mechanism of action of the SARS-CoV-2. A pneumonia patient's bronchoalveolar lavage included a novel virus with an unidentified source. The International Committee on Taxonomy of Viruses designated it as SARS-CoV-2, or severe acute respiratory syndrome coronavirus 2. The associated illness has been designated 2019 Coronavirus Disease and is communicated by coming into touch with those who have it or their fluids (COVID-19). Due to the lack of viable treatments or preventative measures for COVID-19, it is crucial to identify the signalling pathways that are crucial for the pathogenesis of the disease in order to develop new, effective treatments. Adenosine Triphosphate (ATP) release channels found in mammalian vertebrates are called Pannexins (PANX), and they are made up of three proteins. During healthy physiological conditions, cells have a high quantity of ATP in their cytoplasm, which can be released in response to pathological, mechanical, thermal, or ischemia stress or via secretion through pannexin and connexin hemichannels. The increase in extracellular ATP that results from the release of ATP in response to the activation of the PANX1 channel promotes calcium and potassium fluxes. PANX1 channel activation under pathological circumstances is brought on by caspases cleaving the channel's C-terminal tail, elevated intracellular and extracellular Ca2+, hypoxia, immunological responses, and airway defence. Although they lack sequence homology, Connexins (Cxs) and panxs are structurally related. Panx are made up of a cytosolic N-terminal domain, four transmembrane domains with two extracellular loops, and a cytosolic C-terminal domain. Large pore channels known as panxs are formed on the plasma membrane and are known to open during membrane depolarization, changes in intracellular Ca2+ signalling, vasodilation, vasoconstriction, taste perception, airway defence, learning/memory, cellular differentiation, cell death, and during innate and adaptive immune responses. Small signalling molecules, like as ATP, are released into the extracellular environment upon opening of these hemichannels. These surface receptors, which include purinergic receptors, subsequently transmit the signal. It has been established that bicarbonate entry regulates PANX1-mediated ATP release through the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), whose homozygous gene mutations cause Clinical Cystic Fibrosis (CF). When bicarbonate enters the cell, it stimulates the release of ATP and cytochrome c from the mitochondria. This causes caspase 3 to be activated by the cytochrome c, and caspase 3 in turn activates PANX1. PANX1 then opens and releases ATP into the extracellular compartment. Acute respiratory distress syndrome and a more severe hyperinflammatory phase of the disease are usually evident in COVID-19 patients when they first appear with hypoxemia and dyspnea and require supportive Oxygen Therapy (ARDS). In order to ensure that the patient recovers, it is essential to control the early stages of innate immunity. According to some research, immunosuppressive therapy for COVID-19 individuals who have hyperinflammation may slow down the disease's progression as well as viral entrance. In the systemic endothelium (lung microvasculature), lung epithelium, olfactory epithelium, and the parenchyma of numerous tissues throughout the body, there are numerous lines of evidence indicating PANX1 channel activation (and release of ATP) increases inflammatory reactions.