Researchers have discovered that a natural molecule can block a subset of human antibodies to SARS-CoV-2. This may help explain why some COVID-19 patients can become severely ill, despite having high levels of antibodies against the virus.
Researchers from the Francis Crick Institute, in collaboration with researchers at Kings College London, Imperial College London and University College London, discovered that bilirubin and biliverdin could overpower the binding of antibodies to the coronavirus upsurge – and published their research in Science Advances.
“Researchers have discovered that a natural molecule can block a subset of human antibodies to SARS-CoV-2.“
The Crick researchers were involved in tests that comprehend if a person has been exposed to the virus. The scientists found that the SARS-CoV-2 upsurge protein strongly binds to biliverdin.
At UCL, Imperial College London and Kings College London, the researchers found that this molecule reduced antibody binding to the spike. Furthermore, they discovered that biliverdin could suppress the binding of human antibodies by using antibodies and blood sera from previously infected SARS-CoV-2, with some antibodies becoming unsuccessful at neutralising the virus.
In addition, the researchers at the Crick used X-ray crystallography and cryo-electron microscopy to look in detail at the interactions between the antibodies, the spike and biliverdin. They discovered that biliverdin attaches to the spike N-terminal domain and stabilises it so that the spike is unable to open up and expose parts of its structure.
First author and postdoctoral training fellow, Chromatin structure and mobile DNA Laboratory, the Crick, Annachiara Rosa, stated: “When SARS-CoV-2 infects a patient’s lungs it damages blood vessels and causes a rise in the number immune cells. Both of these effects may contribute to increasing the levels of biliverdin and bilirubin in the surrounding tissues. And with more of these molecules available, the virus has more opportunity to hide from certain antibodies. This is a really striking process, as the virus may be benefiting from a side-effect of the damage it has already caused.”
Author and a group leader of Chromatin structure and mobile DNA Laboratory, the Crick, Peter Cherepanov, stated: “In the first months of the pandemic, we were extremely busy churning out viral antigens for SARS-CoV-2 tests. It was a race, as these tests were urgently needed. When we finally found the time to study our green proteins, we expected a mundane answer. Instead, we were astonished to discover a new trick the virus uses to avoid antibody recognition. This is a result of a collaborative effort of several amazing teams working at the Crick and three partner universities, led purely by scientific curiosity.”