As the coronavirus disease (COVID-19) pandemic continues to spread globally, more information about the virus and disease process unravels.
It is well established that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the body through cellular gateways, the angiotensin-converting enzyme 2 (ACE2). Now, a team of scientists revealed that dopamine-release mechanisms in the brain may play a pivotal role in the entry and spread of coronaviruses.
The researchers from Saudi Arabia aimed to investigate the contribution of morbidities and related prescribed medications to COVID-19 associated mortality.
The coronavirus pandemic first emerged in a wet market in Wuhan City, Hubei Province, China, in late December 2019. From there, it has spread to 191 countries and territories worldwide.
Many 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, 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 receptor. Now, the study aims to identify other binding mechanisms of the virus.
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.
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.
Mode of infection of CNS by SARS-CoV-2
The study, which appeared in the Journal of Taibah University Medical Sciences, shows that the SARS-CoV-2 may behave akin to the CNS pathogenic mechanism of JEV and HIV during the early stages of infection.
To arrive at their findings, the researchers from King Abdulaziz University and Taibah University College of Dentistry, Saudi Arabia, studied various clinical scenarios. This way, they can formulate a theoretical framework to better understand the mode of infection of the CNS by SARS-CoV-2.
The 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.
Also, 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.
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.
Further, the elevated production and release of D1-like receptors cause increased expression of cAMP, which causes a lowered innate immune response. On the other hand, the elevated expression of D2-like receptors causes a cytokine storm, which lowers the adaptive immune response.
Next, the research 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.
Hence, SARS-CoV-2 and dopamine could be responsible for impaired ventilation in COVID-19 patients.
Lastly, in a recent study, the researchers 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. All the medicines that act as dopamine antagonists showed the potential to interact with the coronavirus.
The 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.
“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 pandemic coronavirus disease (COVID-19),” the researchers concluded in the study.
Finding an alternative for viral entry can help in the development of vaccines and therapies to help patients infected with SARS-CoV-2, which has caused over 54 million cases worldwide.