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TitleIncorporation of arabinose-CTP and arabinose-UTP inhibits viral polymerases by inducing long pauses.
Journal, issue, pagesJ Biol Chem, Vol. 302, Issue 1, Page 111027, Year 2026
Publish dateDec 9, 2025
AuthorsZiyang Xiao / Arnab Das / Abha Jain / Thomas K Anderson / Craig E Cameron / Jamie J Arnold / David Dulin / Robert N Kirchdoerfer /
PubMed AbstractKey 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 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.
External linksJ Biol Chem / PubMed:41380964 / PubMed Central
MethodsEM (single particle)
Resolution3.31 Å
Structure data

44654

9blf

EMDB-44654, PDB-9blf:
SARS-CoV-2 core polymerase complex inhibited by araCTP
Method: EM (single particle) / Resolution: 3.31 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-MG:
Unknown entry

ChemComp-HF4:
4-amino-1-{5-O-[(S)-hydroxy{[(R)-hydroxy(phosphonooxy)phosphoryl]oxy}phosphoryl]-beta-D-arabinofuranosyl}pyrimidin-2(1H)-one

Source
  • severe acute respiratory syndrome coronavirus 2
  • synthetic construct (others)
KeywordsVIRAL PROTEIN/RNA/INHIBITOR / SARS-CoV-2 / RdRP / Polymerase / araCTP / VIRAL PROTEIN / VIRAL PROTEIN-RNA-INHIBITOR complex

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