A team led by RNA scientist Anne Marie Pyle has compiled the most comprehensive map to date
SARS-CoV-2 relies on its uniqueRNA structures to infect humans and cause COVID-19 disease. But the contribution of these structures to the development of infections and diseases is often underestimated even by scientists, says Pyle, a researcher at the Howard Hughes Medical Institute at Yale University.
By all accounts, if we just focuson proteins encoded in the genome of the virus, we will understand how SARS-CoV-2 works. But for these types of viruses, the RNA structures in the genome can affect their ability to function to the same extent as the encoded proteins.
Anna Marie Pyle, researcher at the Howard Hughes Medical Institute at Yale University
Researchers can now begin to figure out howthese structures help the virus. This information could ultimately lead to new treatments for COVID-19. For example, after scientists have identified the RNA structures that perform key tasks, it will be possible to develop ways to disrupt them and prevent infection.
The genome of SARS-CoV-2, numbering about 30,000 lettersRNA unusually long for an RNA virus. Converting its RNA to 3D form gives SARS-CoV-2 another set of tools with which to compensate for a limited number of genes. “The RNA virus benefits the most in terms of how it uses its genome,” Pyle says.
Colorized electronic scanningmicrograph of a cell (blue) heavily infected with SARS-CoV-2 virus particles (red), isolated from a patient sample. Photo taken at the NIAID Integrated Research Facility (IRF) at Fort Detrick, Maryland.
Credit: NIAID
According to Jeffrey Keeft, StructuralAn RNA biologist and virologist at the University of Colorado, scientists need a roadmap for its genomic landscape to study any RNA virus, in particular SARS-CoV-2. “Dr. Pyle has created a kind of global atlas that is a great starting point for the next round of more targeted experimentation,” he says. “In many ways, this study is scratching the surface of the richness of the RNA structure that is likely to exist in this virus. I suspect there are many surprises in store for us. "
Mapping also representsa preliminary step towards new drugs that can target the RNA structures of the virus. However, the journey can be long. Since 2014, when his lab discovered a nodular structure that dengue and West Nile viruses use to bypass cellular defenses, Kieft has been trying to find a way to neutralize it. He warns that the research community is not fully committed to identifying drugs that disrupt the RNA structure. “This strategy has not been studied and applied in the same way as for proteins,” he says. However, when dealing with a pandemic virus like SARS-CoV-2, "you try everything."
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