Science & Technology

Details of the important SARS-CoV-2 protein are the first step towards new COVID-19 drugs and vaccines

The SARS-CoV-2 (N) (gray) nucleocapsidrin protein (blue) is important in multiple processes of the SARS-CoV-2 infection cycle, including replication and transcription, genomic RNA (gRNA) packaging and protection. Play a role (red). The N protein exists as a dimer in solution and interacts with gRNA primarily through its structured N-terminal domain. N multivalently binds to RNA, and as more N proteins become available, the interaction between RNA and proteins stabilizes and an organized nucleocapsid is produced. Fluorescence imaging of 1-1000 RNA using the Cy3 fluorescent tag shows that FL-N-supplemented RNA-Cy3 is organized and condensed (red punctal background).Credit: OSU Science University

Researchers at Oregon State University Science College have taken an important step towards new drugs and vaccines to fight. COVID-19 (new coronavirus infection) Dive deeper into the interaction with one protein SARS-CoV-2 Genetic material.

The viral nucleocapsid protein, or N protein, plays an important role in the new coronavirus infection cycle and mutates at a relatively slow pace, making it a major target for disease-fighting interventions. Drugs and vaccines built around the action of the N protein have the potential to be very effective and long-term, that is, less susceptible to resistance.

Among the SARS-CoV-2 proteins, the N protein is viral RNAThe biggest partner of. RNA retains the genetic instructions that the virus uses to make more of itself in living cells, such as human cells, and the N protein binds to RNA and protects it.

Published on Biophysics JournalThe findings are an important starting point for additional studies of the interaction of N proteins with their RNA as part of a thorough investigation of the mechanisms of SARS-CoV-2 infection, infection, and regulation.

Elisar Barbar, Professor of Biochemistry and Biophysics at Oregon State University, and PhD. Candidate Heather Masson-Forsyth led the study with the help of undergraduate students Joaquim Rodríguez and Seth Pinkney. Researchers have used a variety of biophysical techniques to measure changes in the size and shape of N proteins when bound to a fragment of genomic RNA (1,000 nucleotides in a 30,000 nucleotide genome).

“The genome is quite large for the virus, and it needs many copies of the N protein to attach to RNA in order to give the virus the spheres it needs to make more copies of itself,” Barber said. Said. “Our study helps to quantify the number of copies of N needed and how close they are to each other when attached to RNA.”

Biophysical studies of N involving large segments of RNA by nuclear magnetic resonance are rare, Barber said. Of Barber Lab. The work of other researchers has generally been limited to much smaller pieces of RNA and smaller pieces of N protein.

Rather than looking at the RNA-binding region of the N protein alone, a view of 1,000 nucleotides allows scientists to bind much more strongly when the protein is a full-length dimer (two copies attached to each other). I was able to learn to do. Identify regions of proteins that are essential for RNA binding.

“We know that complete proteins have a structured part, but in reality they are so flexible that this flexibility is important for RNA binding,” Masson-Forsythe said. Says. “We also know that when N proteins begin to bind to longer RNAs, they result in a diverse collection of bound protein / RNA complexes, as opposed to one binding method.”

Therefore, drugs that impede the flexibility of N-proteins could be one potential tool for pharmaceutical researchers, she said. Another possibility is a drug that destroys any of the protein / RNA complexes that have proven to be of special importance.

References: RNA of the “partially chaotic SARS-CoV-2 nucleocapsidrin protein dimer” by Heather M. Forsythe, Joaquin Rodriguez Galvan, Zhen Yu, Seth Pinckney, Patrick Reardon, Richard B. Cooley, Phillip Zhu, Amber D. Multivalent binding to “. Rolland, James S. Prell, Elisar Barbar, March 29, 2021 Biophysics Journal..
DOI: 10.1016 / j.bpj.2021.03.023

The National Science Foundation Early-concept Grant for Exploratory Research (EAGER) supported this research through the NSF’s Department of Molecular Cell Biological Sciences. The Oregon nuclear magnetic resonance facility used in this study was partially funded by the National Institutes of Health and the MJ Murdoch Charity Trust, and NIH also supported the native mass spectrometric data collection portion of the study. ..

Other researchers on this project were Zhen Yu, Richard Cooley, Phillip Zhu, Patrick Reardon, Oregon, and James Prell and Amber Rolland of the University of Oregon.

Details of the important SARS-CoV-2 protein are the first step towards new COVID-19 drugs and vaccines Details of the important SARS-CoV-2 protein are the first step towards new COVID-19 drugs and vaccines

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