Conserved structures and dynamics in 5′-proximal regions of Betacoronavirus RNA genomesстатья
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Дата последнего поиска статьи во внешних источниках: 19 июня 2024 г.
Аннотация:Betacoronaviruses are a genus within the Coronaviridae family of RNA viruses. They are capable of infecting vertebrates and causing epidemics as well as global pandemics in humans. Mitigating the threat posed by Betacoronaviruses requires an understanding of their molecular div ersity. The development of no v el antivirals hinges on understanding the key regulatory elements within the viral RNA genomes, in particular the 5'-proximalregion, which is piv otal f or viral protein synthesis. Using a combination of cry o-electron microscop y, atomic f orce microscop y, chemical probing,and comput ational modeling , we determined the str uct ures of 5'-proximal regions in RNA genomes of B etacorona viruses from f our subgenera:OC43-CoV, SAR S-CoV-2, MER S-CoV, and R ousettus bat-CoV. We obtained cry o-electron microscop y maps and determined atomic-resolutionmodels for the stem-loop-5 (SL5) region at the translation start site and found that despite low sequence similarity and variable length of thehelical elements it exhibits a remarkable str uct ural conservation. Atomic force microscopy imaging revealed a common domain organization anda dynamic arrangement of str uct ural elements connected with fle xible link ers across all four Betacoronavirus subgenera. Together, these resultsre v eal common features of a critical regulatory region shared between different Betacoronavirus RNA genomes, which may allow targeting ofthese RNAs by broad-spectrum antiviral therapeutics.