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bioRxiv · 10.1101/2022.06.21.496991

Identification of a guanine-specific pocket in the protein N of SARS-CoV-2

Ciges-Tomas, R.·Franco, M. L.·Vilar, M.
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Abstract

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.

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Ciges-Tomas, R., Franco, M. L., Vilar, M.. 2022-06-21. Identification of a guanine-specific pocket in the protein N of SARS-CoV-2. https://doi.org/10.1101/2022.06.21.496991

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