The spotlight on SARS-CoV-2, the virus responsible for COVID-19, has primarily focused on its spike protein, crucial for cell entry. However, scientists from the University of California, San Francisco’s Quantitative Biosciences Institute (QBI), Icahn School of Medicine at Mount Sinai, and University College London have unveiled a more comprehensive picture of the virus’s complexities in a recent Cell publication.
This new research reveals that SARS-CoV-2 employs a variety of proteins beyond the spike protein to suppress the human immune system, shedding light on the virus’s evolution. Dr. Nevan Krogan, founder of QBI and the study’s lead, emphasised the need for a multifaceted approach to combat the virus, similar to how HIV is managed with a combination of therapies.
The findings are an outcome of extensive work by the QBI Coronavirus Research Group, a network of scientists tracking COVID’s evolution and investigating potential therapies since the virus emerged in 2020. Their research has led to over 50 studies and two clinical trials, including one assessing the use of cancer drug plitidepsin for immunocompromised COVID patients.
The study’s key insight is the convergent evolution of different virus strains, where various mutations ultimately lead to the same outcome: suppression of the innate immune response. Dr. Krogan explained that although different strains employ distinct evolutionary trajectories through mutations, they all converge on the same final output, thwarting the immune system’s defence.
To understand this, the researchers cultured healthy lung cells with major virus strains and used computational tools to analyse protein and gene expression changes. They identified select proteins, notably ORF9b, as key players in enabling pre-Omicron variants to suppress innate immunity and invade cells. The original Omicron strain was less effective in evading immunity, possibly suggesting it originated in an immunocompromised patient. Subsequent variants like BA.5 compensated by expressing higher levels of ORF6, enhancing their immune suppression capability.
With a clear understanding of these critical proteins, the researchers are now focused on developing treatments targeting them from multiple angles. These therapies could complement existing approaches, potentially forming a therapeutic “cocktail” that effectively counters SARS-CoV-2.
Dr. Krogan’s dedication to COVID research was recently recognized with the prestigious Research! America’s Discovery | Innovation | Health prize, sponsored by Pfizer, providing further momentum to his ongoing efforts in unravelling the virus’s intricacies and developing effective treatments.