9BLF

SARS-CoV-2 core polymerase complex inhibited by araCTP

Summary for 9BLF

• Entry DOI: 10.2210/pdb9blf/pdb
• Related: 9PYW 9PYZ 9PZ0
• EMDB information: 44654
• Descriptor: RNA-directed RNA polymerase nsp12, Non-structural protein 8, Non-structural protein 7, ... (8 entities in total)
• Functional Keywords: sars-cov-2, rdrp, polymerase, aractp, viral protein, viral protein-rna-inhibitor complex, viral protein/rna/inhibitor
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 6
• Total formula weight: 186914.20

Authors

Anderson, T.K.,Xiao, Z.,Kirchdeorfer, R.N. (deposition date: 2024-04-30, release date: 2025-05-14, Last modification date: 2026-05-27)

Primary citation

Xiao, Z.,Das, A.,Jain, A.,Anderson, T.K.,Cameron, C.E.,Arnold, J.J.,Dulin, D.,Kirchdoerfer, R.N.
Incorporation of arabinose-CTP and arabinose-UTP inhibits viral polymerases by inducing long pauses.
J.Biol.Chem., 302:111027-111027, 2026

PubMed Abstract: Key to supporting human health in the face of evolving viruses is the development of novel antiviral drug scaffolds with the potential for broad inhibition of viral families. Nucleoside analogs are a key class of drugs that have demonstrated potential for the inhibition of several viral species. Here, we evaluate arabinose nucleotides (ara-NTP) as inhibitors of the severe acute respiratory syndrome coronavirus 2 and poliovirus polymerases using biochemistry, biophysics, and structural biology. Ara-NTPs compete poorly with their natural counterparts for incorporation into RNA by viral polymerases. However, upon incorporation, ara-NMPs induce long polymerase pausing during both severe acute respiratory syndrome coronavirus 2 and poliovirus polymerase RNA elongation. Our studies suggest that following ara-NMP incorporation, additional nucleotide incorporation is inhibited at the catalytic step.

PubMed: 41380964
DOI: 10.1016/j.jbc.2025.111027

Experimental method

ELECTRON MICROSCOPY (3.31 Å)