Study reveals potentially drug-induced assembly and replication process of SARS-Cov-2
Of all the proteins in the SARS-CoV-2 virus (the pathogen that causes COVID-19), the spike protein is the one that receives the most attention. This attention is well deserved – the spike protein is essential for latching onto cells and infecting a host, and the three FDA-approved COVID-19 vaccines focus on the spike protein. While the initial invasion of a virus into a host is certainly an important step in the viral life cycle, once inside the cell, the virus must replicate in order to survive. And that’s where the core protein, or N protein, comes in.
The N protein is the most abundant protein in the SARS-CoV-2 virus. Its job is to pack the viral genome into structures called ribonucleoprotein particles, which are then loaded into nascent virions that are released from an infected cell to wreak havoc in surrounding cells. Due to its essential role in viral assembly and replication, the N protein is a promising immunological target for anti-COVID-19 strategies.
With the inevitable increase in SARS-CoV-2 variants, multi-pronged strategies that can prevent disease or limit the severity of COVID-19 are vital. The N protein is an essential player in viral assembly, but the exact way in which this protein packages the SARS-CoV-2 genome is not known. If we could better understand this process, we could identify targets that would stop viral replication, offering an additional approach for COVID-19 vaccines or treatments. “
Peter Schuck, Ph.D., Researcher in the Dynamics of Macromolecular Assembly Section, National Institute of Biomedical Imaging and Bioengineering
Schuck’s research, recently published in iScience, studies how the N protein interacts with oligonucleotides – short stretches of DNA and RNA – to demystify how the viral genome is packaged. Using biophysical methods, Schuck and his colleagues found that when the N protein interacts with nucleotides of sufficient length, it assumes a shape that promotes interactions with other proteins.
Additionally, when the N protein binds to multiple copies of itself and to long stretches of oligonucleotides, it can condense into highly concentrated droplets which are believed to eventually allow the formation of ribonucleoprotein particles. Targeting interactions between the N protein and its binding partners could be a viable way to inhibit viral replication of SARS-CoV-2, Schuck said.
“Our study is just one small piece of the puzzle posed by the SARS-CoV-2 viral life cycle,” said Schuck. “We now have some additional clues as to how the N protein initiates the assembly of ribonucleoprotein particles, an important – and potentially drug – part of viral replication.”
National Institute of Biomedical Imaging and Bioengineering