Identifying Human Proteins Essential for Coronavirus Replication Offers New Therapeutic Avenues

Recent research from Scripps Research has identified a range of human proteins that play crucial roles in the replication of SARS-CoV-2, the virus responsible for COVID-19. Despite advancements in vaccines and treatments, the emergence of new variants continues to challenge global health efforts. This new study, published in PLOS Biology, highlights the potential for novel treatment strategies that target human proteins instead of the virus itself.

The research team employed a genome-wide small interfering RNA (siRNA) screening technique to discover which human proteins SARS-CoV-2 requires for its lifecycle, from cell entry to replication and release of new viral particles. They identified 32 proteins critical for the initial stages of infection, alongside 27 proteins utilized in later stages, revealing both established and novel cellular pathways exploited by the virus.

The lead researcher emphasized the importance of understanding the virus's interaction with host cells. By targeting human proteins that coronaviruses depend on, the development of broad-spectrum therapies could be possible, providing effective treatments not only for current strains but also for future variants.

Among the proteins identified, two stand out as potential drug targets. The first, perlecan, is a large protein with sugar chains found in the extracellular matrix surrounding cells. It was found that SARS-CoV-2's spike protein can bind to these sugar chains, facilitating viral entry into human cells. Inhibiting this interaction may offer a method to prevent infection.

The second protein, Baculoviral IAP Repeat Containing 2 (BIRC2), is involved in cellular inflammatory responses. Experiments with human cell cultures and infected mice demonstrated that compounds known as second mitochondria-derived activators of caspases (Smac) mimetics, originally designed for cancer treatment, significantly reduced viral levels by targeting BIRC2.

Furthermore, the research tested the efficacy of these human proteins against other coronaviruses, including SARS-CoV-1 and MERS-CoV. Of the 47 proteins analyzed, 17 were found to be commonly used by all three viruses, indicating that therapies designed to block these proteins could be effective against various coronaviruses, past and present.

This approach has the potential to create antiviral drugs that could preemptively address future coronavirus outbreaks, thus reducing the risk of resistance due to viral mutations. Moving forward, the research team plans to investigate if these host proteins are also utilized by other respiratory pathogens such as influenza and RSV, while continuing to assess the safety and efficacy of the compounds identified.