Why do some people with Covid-19 develop severe inflammation? A new study addresses this question by looking at the molecular structure and sequence of the SARS-CoV-2 spike protein, the key part of the virus that causes Covid-19. The study uses computational modelling to zero in on a part of the SARS-CoV-2 spike protein that may act as a “super-antigen”. It proposes that this part kicks the immune system into overdrive leading to inflammatory syndrome.
The study is published in the Proceedings of the National Academy of Sciences.
Symptoms of a newly identified condition in paediatric Covid-19 patients, known as Multisystem Inflammatory Syndrome in Children (MISC), include persistent fever and severe inflammation that can affect a host of bodily systems. While rare, the syndrome can be serious or even fatal.
Researchers Moshe Arditi (Cedars Sinai Medical Center) and Ivet Bahar (University of Pittsburgh School of Medicine) searched for features of the SARS-CoV-2 virus that might be responsible for MIS-C.
They created a computer model of the interaction between the SARS-CoV2 spike protein and the receptors on human T cells. These T cells are part of the immune system and normally help the body fight off infection, but when they are activated in abnormally large quantities, they produce massive amounts of inflammatory cytokines, leading to a “cytokine storm“.
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The computer model identified a specific region on the spike protein with super-antigenic features — which can lead to an abnormal immune response. The researchers compared this region to a bacterial protein that causes toxic shock syndrome and found striking similarities in both sequence and structure.
Also, the proposed SARS-CoV-2 super-antigen showed a high affinity for binding with T cell receptors — the first step towards a runaway immune response.
The discovery of protein-level similarities between SARS-CoV-2 and the bacterial structure that causes toxic shock syndrome, the researchers said, may have opened up new avenues for treating not only MIS-C patients, but also adults with Covid-19 infection experiencing cytokine storm.
The researchers also collaborated with scientists studying adult Covid-19 patients in Germany and found that those who experienced severe symptoms had a T-cell response similar to what is seen in people exposed to super-antigens and very different from the T cell response in patients who had only mild symptoms.
Source: Cedars-Sinai Medical Center
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