There Was a Reason Why Coronavirus Spreads Rapidly [Now Science]

COVID-19, like the severe acute respiratory syndrome (SARS) coronavirus, has spread worldwide in a short period of time as a global pandemic. The mechanism of why it replicates rapidly and spreads rapidly has not been clarified.



A research team at the Korea Advanced Institute of Science and Technology (KAIST) has discovered the mechanism of rapid acceleration of the replication process of the core enzyme protein (helicase) of the coronavirus and its transmission. This suggests new possibilities for the development of virus vaccines and treatments.



KAIST (President Kwang-hyung Lee) announced on the 17th that the research team of Professor Kwang-rok Lee of the Department of Life Sciences has clarified the mechanism of its operation. According to the research results, the nsp13 protein (helicase of the SARS coronavirus. An enzyme important for the essential gene replication and transcription process for the virus to proliferate) has two activities, which produce a synergistic effect, and through this, it has discovered the mechanism of its operation of promoting RNA replication, the genetic material of the SARS coronavirus.



Schematic diagram of cooperative unfolding activity through two methods in the substrate of the nspl3 protein. [Photo = KAIST]



The first helicase activity is an enzyme that unwinds double-stranded nucleic acids such as DNA or RNA into single strands. It promotes replication or transcription processes. The second RNA chaperone activity is a protein that helps with the correct folding and unfolding of nucleic acid structures, and it corrects incorrect RNA or improves stability to help with RNA metabolism within cells.



In order for coronaviruses to spread quickly, it is essential to quickly replicate the genetic material of the virus and produce and assemble its constituent proteins.



The research team discovered that the nsp13 protein rapidly promotes the gene replication process with existing helicase activity and a previously unknown new chaperone activity, although it was not known why the first step, RNA replication of genetic material, occurs faster than other



viruses. The nsp13 protein is genetically well-conserved and is an important target for vaccines or infection treatments that respond to various mutant coronaviruses. The exact mechanism of action was not fully understood.



The research team discovered that nsp13 helicase uses the chemical energy generated by breaking down ATP (adenosine triphosphate) to unwind the coiled structure of RNA, the genetic material, into single strands, generating ADP (adenosine diphosphate) as a byproduct.



The ADP generated at this time activates the chaperone function when it recombines with nsp13, further destabilizing the RNA secondary structure.



In conclusion, they have discovered a new mechanism of action in which helicase activity and chaperone activity simultaneously cooperate in space and time to promote RNA replication.



Professor Kwang-Rok Lee said, "This study is a new discovery that helicase, a representative nucleic acid-enzyme protein, exhibits chaperone activity through ADP." He added, "We expect that this will broaden our understanding of the functional diversity of helicase and provide a clue to the development of effective treatments and vaccines to respond to various mutations of the SARS coronavirus."



This study (paper title: A novel ADP-directed chaperone function facilitates the ATP-driven motor activity of SARS-CoV helicase) was published on January 29th in the online version of the international academic journal 'Nucleic Acids Research' with Dr. Jeongmin Yoo as the first author.





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