Published: 10th October 2020
Blocking immune system pathway may stop COVID-19: Johns Hopkins study
Based on their findings published in the journal 'Blood', the researchers believe that inhibiting the protein known as Factor D will also curtail the potentially deadly inflammatory reactions
As the world waits eagerly for an effective vaccine against the Covid-19 virus, researchers are also focusing on better understanding of how the virus attacks the body in the quest for other means of stopping its devastating impact. The key to one possibility -- blocking a protein that enables the virus to turn the immune system against healthy cells -- has been identified in a recent study by a team of Johns Hopkins University researchers.
Based on their findings published in the journal 'Blood', the researchers believe that inhibiting the protein known as Factor D will also curtail the potentially deadly inflammatory reactions that many patients have to the virus. Scientists already know that spike proteins on the surface of the SARS-CoV-2 virus -- making the pathogen look like the spiny ball from a medieval mace -- are the means by which it attaches to cells targeted for infection.
To do this the spikes first grab hold of heparan sulfate, a large, complex sugar molecule found on the surface of cells in the lungs, blood vessels and smooth muscle making up most organs. Facilitated by its initial binding with heparan sulfate, SARS-CoV-2 then uses another cell-surface component, the protein known as angiotensin-converting enzyme 2 (ACE2), as its doorway into the attacked cell. The Johns Hopkins medicine team discovered that when SARS-CoV-2 ties up heparan sulfate, it prevents Factor H from using the sugar molecule to bind with cells.
Factor H's normal function is to regulate the chemical signals that trigger inflammation and keep the immune system from harming healthy cells. Without this protection, cells in the lungs, heart, kidneys and other organs can be destroyed by the defence mechanism nature intended to safeguard them. "Previous research has suggested that with tying up heparan sulfate, SARS-CoV-2 activates a cascading series of biological reactions -- what we call the alternative pathway of complement or APC -- that can lead to inflammation and cell destruction if misdirected by the immune system at healthy organs," said the study's senior author Robert Brodsky.
The APC is one of the three chain reaction processes involving the splitting and combining of more than 20 different proteins -- known as complement proteins -- that usually gets activated when bacteria or viruses invade the body. In a series of experiments, the research team used normal human blood serum and three sub-units of the SARS-CoV-2 spike protein to discover exactly how the virus activates the APC, hijacks the immune system and endangers normal cells.
They discovered that two of the sub-units called S1 and S2 are the components that bind the virus to heparan sulfate -- setting off the APC cascade and blocking Factor H from connecting with sugar -- and in turn disabling the complement regulation by which Factor H deters a misdirected immune response. "We found that by blocking another complement protein known as Factor D which works immediately upstream in the pathway from Factor H, they were able to stop the destructive chain of events triggered by SARS-CoV-2," the authors wrote.