COVID-19 Virus Secretly Targets Brain: How It Infects Through ‘Back Door’

COVID-19 Virus Secretly Targets Brain: How It Infects Through ‘Back Door’

SARS-CoV-2, the virus responsible for the COVID-19 pandemic, continues to surprise scientists with its ability to infiltrate the human body in unexpected ways. A recent mouse study has shed light on how the virus may preferentially use a “back door” to infect the brain, potentially explaining the neurological symptoms that many COVID-19 patients experience.

Neurological symptoms such as fatigue, dizziness, brain fog, and loss of smell or taste have been reported by a significant number of individuals who have been infected with SARS-CoV-2. These symptoms suggest that the virus is able to enter the central nervous system, but the exact mechanism by which it does so has been unclear until now.

In a groundbreaking study published in the journal Nature Microbiology, researchers identified mutations in the virus’s spike protein that may play a crucial role in its ability to infect the brain. The spike protein is responsible for binding to a molecule called ACE2 on the surface of human cells, allowing the virus to gain entry.

Study co-author Judd Hultquist, an assistant professor of infectious diseases at Northwestern University in Chicago, explained, “The SARS-CoV-2 spike protein coats the outside of the virus and allows it to enter a cell. Normally, the virus can enter the cell in two ways: either at the cell surface (through the front door) or internally after it is taken up into the cell (through the back door).”

The researchers found that a specific part of the spike protein, known as the furin cleavage site, plays a crucial role in determining how the virus enters cells. Mutations in this site can alter the virus’s ability to use the front door, forcing it to rely on the back door route instead.

According to Hultquist, “Cells in the upper airways and lungs are highly susceptible to SARS-CoV-2, which can enter these cells through the front and back doors. To reach and replicate successfully in the brain, it seems like the virus has to enter through the back door. Deleting the furin cleavage site makes the virus more likely to use this pathway — and more likely to infect brain cells.”

To investigate this further, the researchers conducted experiments on genetically engineered mice that were modified to produce human ACE2. After infecting these mice with SARS-CoV-2, the researchers analyzed virus samples taken from lung and brain tissue and sequenced the viral genomes.

The results of the study revealed that mice infected with the mutated virus showed a higher level of infection in the brain compared to those infected with the normal virus. The researchers observed a particularly high rate of infection in cells of the hippocampus and premotor cortex, regions of the brain associated with memory and movement.

While the study provides valuable insights into how SARS-CoV-2 may target the brain, it is important to note that the findings were based on experiments conducted in mice. Further research is needed to determine whether the virus behaves in a similar manner in humans.

Matthew Frieman, a professor of microbiology and immunology at the University of Maryland, emphasized the importance of confirming these findings in human samples. He stated, “As researchers target neuronal inflammation for therapy against long-COVID symptoms, understanding how the virus replicates there in the first place is of critical importance.”

Hultquist also expressed interest in exploring why mutations in the furin cleavage site make the virus more likely to infect the brain. He noted, “We show in the study that normal SARS-CoV-2 can replicate in the brain if it is directly injected, which suggests that loss of the furin cleavage site is important for travel to the brain. How exactly this works remains a mystery.”

Despite the unanswered questions, the research opens up new possibilities for developing treatments to address the neurological effects of COVID-19. Hultquist suggested that targeting the back door pathway through which the virus enters the brain could be a promising approach.

“Knowing that the virus needs the back door to infect the brain provides unique opportunities to stop it,” Hultquist explained. “Small molecules that block this pathway may be particularly effective at preventing infection of the brain and the complications that arise. The next challenge will be to figure out not only which drugs may be best able to do this, but also which ones can get to the brain.”

In conclusion, the study highlights the complex ways in which SARS-CoV-2 interacts with the human body and underscores the importance of further research to fully understand the virus’s behavior. By unraveling the mysteries of how the virus targets the brain, scientists may be able to develop targeted therapies to mitigate the neurological effects of COVID-19 and improve patient outcomes.