BREAKING! Coronavirus News: Saudi Arabia Study Shows That Dopamine Receptors Might Be Targeted By SARS-COV-2 Coronavirus
: A new study by researchers from King Abdulaziz University-Saudi Arabia and Taibah University-Saudi-Arabia alarmingly points out that the SARS-CoV-2 coronavirus could also target the dopamine and dopaminergic receptors and co-receptors and that dopamine-release mechanisms in the central nervous system may play a major role in the entry and propagation of the SARS-CoV-2 coronaviruses.
The study findings were published in the peer-reviewed Journal of Taibah University Medical Sciences
Day by day, new revelations are emerging about the SARS-CoV-2 coronavirus and its pathogenesis.
It is well established that the SARS-CoV-2 enters the body through cellular gateways using a multitude of receptors not just the angiotensin-converting enzyme 2 (ACE2).
A team of scientists now reveal that dopamine-release mechanisms in the brain may play a pivotal role in the entry and spread of coronaviruses.
The study from Saudi Arabia aimed to investigate the contribution of morbidities and related prescribed medications to COVID-19 associated mortality.
Numerous research studies are currently addressing the potential impact of SARS-CoV-2 on the brain based on reports of neural manifestations. Other patients who develop severe COVID-19 experience a cytokine storm ie a severe immune reaction in which the body releases too many cytokines into the blood too quickly. On rare occasions, viral infections also trigger neurological symptoms.
It is also known that common binding mechanisms of SARS-CoV-2 in the body are through the ACE 2 receptors but at the same time a vareity of other receptors have also been identified. This study aims to identify other binding mechanisms of the virus.
Based on past studies it is also known that dopaminergic receptors are involved in the entry of many viruses. For instance, increased dopamine levels can enhance the onset of the human immunodeficiency virus (HIV) and related central nervous system (CNS) infections by inducing the expression of HIV entry co-receptors, enabling the virus to evade the immune system. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0108232
Yet another example is the Japanese encephalitis virus (JEV), a flavivirus related to Dengue, yellow fever, and West Nile viruses. JEV is spread by mosquitoes and can disrupt the blood-brain barrier and cause encephalitis. It also exploits dopamine signaling to accelerate the infectious process. https://www.frontiersin.org/articles/10.3389/fmicb.2017.00651/full
This new study shows that the SARS-CoV-2 may behave akin to the CNS pathogenic mechanism of JEV and HIV during the early stages of infection.
Based on these findings, the study team says that SARS-CoV-2 may mimic the behavioural CNS pathogenic mechanism of JEV and HIV during the early stages of COVID-19. These
are some of their assumptions:
-SARS-CoV-2 may exploit dopaminergic receptors to improve its life-cycle, increasing viral entry chances.
-Dopamine-agonist drugs may disrupt the respiratory system by affecting the carotid body chemosensitivity, resulting in decreased oxygen levels and worsens ventilation response.
-SARS-CoV-2 hinders the innate and adaptive immune responses via dopamine-mediated disruption of intracellular biosynthesis
Numerous clinical observations support this hypothesis. First, the neurological manifestations often appear after the diagnosis of the COVID-19, similar to some neurotropic microbial infections. https://www.sciencedirect.com/science/article/abs/pii/S0889159120303573
Dopaminergic receptors can enhance the chance of binding of some viruses to the CNS to initiate viral encephalitis in the early stages of viral infection. An example of this mechanism is D2DR in cases of HIV and JEV encephalopathy. Moreover, the viral life-cycle of SARS-CoV-2 may be enhanced in the presence of high levels of catecholamine, possibly by binding to dopaminergic receptors and increasing the chance of viral entry.
Entry phase of the virus: it is possible that after the initial binding of SARS-CoV-2 to ACE2 receptors, the Spike-like protein of the virus binds to dopaminergic receptors of neighbouring cells. The presence of dopamine receptors in the brain plays an integral regulatory role in local immunity (e.g. lymphocytes, cytokines). Cytokines or neurokines have a regulatory function in both nervous and the immune systems. In addition, dopamine at certain concentrations can inhibit the lymphocytic function. B. The influx of dopamine causes further decrease in both the innate and adaptive immunity that helps increasing the viral load. This leads to more neural manifestations, such as encephalopathy, fatigue, dizziness, unconsciousness, among others. Increased production of D1-like receptors (D1) results in increased expression of cAMP, which causes a decrease in the innate immune response; whereas high expression of D2-Like receptors (D2) results in a cytokine storm that leads to a reduction of the adaptive immune response.
In order to arrive at their findings, the researchers studied various clinical scenarios. This way, they could formulate a theoretical framework to better understand the mode of infection of the CNS by SARS-CoV-2.
The study team noted that it is possible that after the initial binding or attachment of the SARS-CoV2 to ACE2 receptors, the spike protein of the virus binds to dopaminergic receptors of adjacent cells. Since the brain has dopamine receptors, it plays an integral regulatory role in local immunity, such as the release of lymphocytes and cytokines.
Furthermore, dopamine at certain concentrations can disrupt lymphocytic function. When there is an influx of dopamine, it further decreases both innate and adaptive immunity. This causes neural symptoms, including fatigue, dizziness, encephalopathy, and loss of consciousness, among others.
As dopamine is also a regulator of immune function. The virus may manipulate the immune system by elevating the levels of dopamine to help them enter cells.
Importantly the elevated production and release of D1-like receptors cause increased expression of cAMP, which causes a lowered innate immune response. https://www.atsjournals.org/doi/full/10.1165/rcmb.2008-0091TR
On the other hand, the elevated expression of D2-like receptors causes a cytokine storm, which lowers the adaptive immune response. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0108232 https://www.karger.com/Article/Abstract/342140
A possible explanation is the exacerbation of pro-inflammatory responses that will worsen the pathogenic condition.Here, the exhaustion of T-cells could have led to the progression of the COVID-19. Therefore, in both innate and adaptive responses, the presence of SARS-CoV-2 infection will result in high interleukin (IL)-6 levels.
In keratinocytes, “dopamine stimulated the production of IL-6 and IL-8 in a concentration-dependent manner”. Thus, these findings suggest that dopamine plays a primary role in reducing the host immunity and increasing the chance for severe complications. https://www.karger.com/Article/Abstract/342140
The study team also revealed that elevated dopamine levels reduce oxygen levels, which is often seen in patients with COVID-19. Dopamine can blunt the ventilatory response of the human basal carotid body activity to hypoxia. https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.1007.1217&rep=rep1&type=pdf
Thus it is apparent that the SARS-CoV-2 coronavirus and dopamine could be responsible for impaired ventilation in COVID-19 patients.
In a recent study, the study team noted three drugs among the ten tested drugs in a study that influences dopamine secretion. One of the drugs was shown to have the most beneficial outcome after Chinese researchers tested over 2,000 drugs in vitro. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147283/
Significantly all the drugs that act as dopamine antagonists showed the potential to interact with the SARS-CoV-2 coronavirus. https://jamanetwork.com/journals/jamaneurology/article-abstract/2764549
The study team has found that dopamine-released mechanisms in the brain may play an imperative role in the entry and spread of coronaviruses, particularly SARS-CoV-2.
The study team concluded, “This study emphasizes the need for a thorough and urgent investigation of the dopamine-release pathways in the central nervous system. These efforts will help find a definitive cure for the COVID-19 disease.”
They added, “A review of the composition of drugs used for chronic illnesses must be undertaken urgently to avoid severe complications accompanying COVID-19. Based on our assumptions, there is a strong link between the amount of dopamine controlled by these drugs and the severity of COVID-19 complications.”
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