Beneath the SARS-CoV-2 membrane and its spikes lurks a squiggle of genetic material, or RNA, enveloped by a protein that acts like bubble wrap to protect the genetic material. This protein also acts as a "hotbed" for multiple interactions to control the infected cell.
Transmission electron micrograph of SARS-CoV-2 virus particles, isolated from a patient. Image captured and color-enhanced at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID Through atomic-resolution studies conducted by University of Colorado Anschutz Medical Campus researchers and others, how this protein interacts with its targets to regulate multiple functions, such as viral replication, is now becoming clearer. Getting at the root of SARS-CoV-2 infection—and searching for vulnerabilities to exploit therein, potentially to curb infections from more coronaviruses—is a research interest of Elan Eisenmesser, Ph.D., an associate professor in the Department of Biochemistry and Molecular Genetics at the University of Colorado School of Medicine. This "hotbed" of interactions sits on the nucleocapsid, one of four structural proteins encoded by SARS-CoV-2. The other three proteins are the spike, membrane and envelope proteins. The nucleocapsid is made up of 419 residues with distinct domains that include a well-folded N- and C-terminal domain. However, over half of the nucleocapsid protein (N protein) comprises largely dynamic, or flexible, regions made of spaghetti-like sections, referred to as "intrinsically disordered regions." Eisenmesser's team has been studying all of the regions of the nucleocapsid protein to better understand how N proteins play a role in packaging viral RNA and manipulating host cell machinery. Part of the nucleocapsid's manipulative behavior, Eisenmesser said, could be to prevent the host cell's ability to mount an immune response, basically by blocking proteins from carrying out their virus-fighting jobs. Study expands to whole protein Eisenmesser co-authored a study, spearheaded by Jasmina S. Redzic, Ph.D., and Eunjeong Lee, Ph.D., and published in the Journal of Molecular Biology (July 2021), which explained the interactions of SARS-CoV-2 N protein's N-terminal domain with several biological…