Incorporation of arabinose-CTP and arabinose-UTP inhibit viral polymerases by inducing long pauses.

Incorporation of arabinose-CTP and arabinose-UTP inhibit viral polymerases by inducing long pauses.

Publication date: Dec 09, 2025

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 SARS-CoV-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 SARS-CoV-2 and poliovirus polymerase RNA elongation. Our studies suggest that following ara-NMP incorporation, additional nucleotide incorporation is inhibited at the catalytic step.

Concepts Keywords
Biophysics cryo‐electron microscopy
Compete magnetic tweezers
Inhibitors nucleoside/nucleotide analogue
Polymerase poliovirus
Viruses SARS-CoV-2
single‐molecule biophysics
viral polymerase

Semantics

Type Source Name
disease MESH face
drug DRUGBANK Methyl pyrrolidone

Original Article

(Visited 1 times, 1 visits today)

Leave a Comment

Your email address will not be published. Required fields are marked *