Most COVID-19 cases are mild, but many still lead to life-threatening complications. Severe cases feature an overactive immune response that causes dangerous inflammation. This inflammation affects many different tissues and cell types, including uninfected ones, and resembles that seen in some autoimmune diseases. It’s not clear why SARS-CoV-2 can cause such inflammation while other coronaviruses responsible for common colds don’t.
One way the immune system fights viruses is by breaking down the viral proteins into small fragments called peptides. An NIH-funded research team—led by Dr. Gerard Wong at the University of California, Los Angeles, in collaboration with Richard L. Gallo at the University of California, San Diego—investigated whether these peptides could continue to activate the immune system. Their results were published in Proceedings of the National Academy of Sciences on February 6, 2024.
The team used machine learning to search SARS-CoV-2 proteins for fragments that resemble molecules called antimicrobial peptides (AMPs). The body makes these molecules as part of its defense against infections. Certain AMPs can bind to double-stranded RNA (dsRNA), which is produced during some viral infections. The resulting AMP-dsRNA complexes have been shown to trigger inflammation and have been implicated in autoimmune conditions such as lupus, rheumatoid arthritis, and psoriasis. Among the SARS-CoV-2 AMP-like fragments, the team looked for those that carried a strong positive electric charge. This would allow them to bind dsRNA, which is negatively charged.