Scientists have identified 65 human immune genes activated during SARS-CoV-2 infection. This finding provides valuable insights into why some individuals experience more severe COVID symptoms than others and paves the way for novel therapeutic interventions.
The study, published in Molecular Cell, was led by Sumit K. Chanda and colleagues from Sanford Burnham Prebys. They found that interferon-stimulated genes, or ISGs, play a key role in determining COVID severity. Interferons are signaling proteins that are central to the body’s ability to protect itself from viral attacks.
"We wanted to gain a better understanding of the cellular response to SARS-CoV-2, including what drives a strong or weak response to infection," said Chanda.
"We've gained new insights into how the virus exploits the human cells it invades, but we are still searching for its Achilles heel so that we can develop optimal antivirals."
The researchers found that a panel of 65 ISGs controlled the dynamics of SARS-CoV-2 infection in a multifaceted way, inhibiting the coronavirus’ ability to invade cells and stopping the virus from replicating in human cells.
"We identified eight ISGs that inhibited both SARS-CoV-1 and CoV-2 replication in the subcellular compartment responsible for protein packaging, suggesting this vulnerable site could be exploited to clear the viral infection," said the study’s first author, Laura Martin-Sancho.
"This is important information, but we still need to learn more about the biology of the virus and investigate if genetic variability within these ISGs correlates with COVID-19 severity."
The team plans to expand the study by investigating the infection dynamics of SARS-CoV-2 variants, focusing on how these may undercut vaccination efforts. "It's vitally important that we don't take our foot off the pedal of basic research efforts now that vaccines are helping control the pandemic," commented Chanda.