Domestic researchers have found clues that can explain why the coronavirus replicates rapidly. Coronaviruses that cause severe acute respiratory syndrome (SARS) and coronavirus disease (COVID-19) have spread globally in a short period; however, the exact mechanism of their fast replication has not been fully understood.
A research team led by Lee Gwang-rok, a professor in the Department of Biological Sciences at the Korea Advanced Institute of Science and Technology (KAIST), noted on the 17th that the nsp13 protein, essential for the replication of SARS coronavirus, possesses two activities that work synergistically, thereby promoting the replication of the genetic material, ribonucleic acid (RNA). The research results were published online in the international journal Nucleic Acids Research on the 29th of last month.
For the virus to spread, it is essential to quickly replicate its genetic material and produce proteins to assemble them. A specific protein plays a crucial role in this process. Among them, the nsp13 protein is key to the replication of coronaviruses. First, it functions as a helicase, unwinding the double-stranded structures of deoxyribonucleic acid (DNA) and RNA into single strands, much like opening and closing a zipper, thereby facilitating the processes of gene replication or transcription. It also plays a role as a 'Shaperon,' helping the correct folding and unfolding of nucleic acid structures. This function aids in correcting faulty RNA or enhancing stability to support the metabolic processes of RNA within cells.
The research team confirmed the specific mechanism by which the nsp13 protein rapidly promotes gene replication through experiments. First, nsp13 unwinds the coiled structure of RNA into a single strand using energy derived from the breakdown of adenosine triphosphate (ATP), a cellular energy source. Adenosine diphosphate (ADP) is produced as a byproduct in this process. When ADP binds again to the nsp13 protein, its Shaperon function is activated, facilitating RNA replication further. In other words, the helicase and Shaperon functions work together, exponentially increasing the virus's replication.
It was previously known that nsp13 plays an important role in viral replication, but it was unclear exactly how it functions. This study revealed that the two functions of nsp13 collaborate to rapidly amplify the virus. The research is expected to provide new clues for developing vaccines and treatments against coronaviruses with many mutations. It could also assist in finding therapeutic targets to slow down the rate of viral replication.
Professor Lee Gwang-rok stated, "This study confirmed that the representative nucleic acid-enzyme protein helicase exhibits Shaperon activity through ADP," adding, "It broadens our understanding of the helicase function and is expected to provide clues for developing effective treatments and vaccines against various mutations of SARS coronavirus."
References
Nucleic Acids Research (2025), DOI: https://doi.org/10.1093/nar/gkaf034