PT  - JOURNAL ARTICLE
AU  - J. Rafael Ciges-Tomas
AU  - María Luisa Franco
AU  - Marçal Vilar
TI  - Identification of a guanine-specific pocket in the protein N of SARS-CoV-2
AID  - 10.1101/2022.06.21.496991
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.06.21.496991
4099  - http://biorxiv.org/content/early/2022/06/21/2022.06.21.496991.short
4100  - http://biorxiv.org/content/early/2022/06/21/2022.06.21.496991.full
AB  - The SARS-CoV-2 nucleocapsid protein (N) is responsible for RNA binding. Here we report the crystal structure of the C-terminal domain (NCTD) in open and closed conformations and in complex with guanine triphosphate, GTP. The crystal structure and biochemical studies reveals a specific interaction between the guanine, a nucleotide enriched in the packaging signals regions of coronaviruses, and a highly conserved tryptophan residue (W330). In addition, EMSA assays with SARS-CoV-2 derived RNA hairpin loops from a putative viral packaging sequence showed the preference interaction of the N-CTD to RNA oligonucleotides containing G and the loss of the specificity in the mutant W330A. Here we propose that this interaction may facilitate the viral assembly process. In summary we have identified a specific guanine-binding pocket in the N protein that may be used to design viral assembly inhibitors.Competing Interest StatementThe authors have declared no competing interest.