Publication date: Oct 07, 2025
SARS-CoV-2’s remarkable resistance to nucleotide analog antivirals such as remdesivir, which thwarts RNA synthesis by inhibiting viral polymerase (RdRp), challenges available therapies. We reveal that remdesivir incorporation destabilizes RdRp-RNA complex while enhancing RNA binding to the proofreading exoribonuclease (ExoN), facilitating remdesivir excision. Conserved ExoN determinants for remdesivir recognition and excision underpin ExoN-mediated resistance across all coronaviruses. These findings inform the design of next-generation antivirals and combination therapies capable of overcoming ExoN-mediated resistance.
Semantics
| Type | Source | Name |
|---|---|---|
| drug | DRUGBANK | Adenosine phosphate |
| drug | DRUGBANK | L-Alanine |
| disease | MESH | COVID-19 |
Original Article
(Visited 5 times, 1 visits today)