9Q1J

Cryo-EM structure of SARS-CoV-2 nsp10-nsp14 E191A mutant-T20P14-R complex

Summary for 9Q1J

• Entry DOI: 10.2210/pdb9q1j/pdb
• EMDB information: 72127
• Descriptor: Non-structural protein 10, Proofreading exoribonuclease, T20P14-R RNA, ... (6 entities in total)
• Functional Keywords: sars-cov-2, replication and transcription, mismatch, proofreading exoribonuclease, viral protein, viral protein-rna complex
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 12
• Total formula weight: 329252.43

Authors

Yang, Y.,Liu, C.,Liu, B. (deposition date: 2025-08-14, release date: 2025-09-24, Last modification date: 2025-10-15)

Primary citation

Yang, Y.,Li, Y.,Becker, S.T.,Khan, A.,Luo, G.,Liu, B.,Liu, C.
Molecular basis of SARS-CoV-2 proofreading enzyme-mediated resistance to remdesivir.
Proc.Natl.Acad.Sci.USA, 122:e2519755122-e2519755122, 2025

PubMed Abstract: 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.

PubMed: 41032524
DOI: 10.1073/pnas.2519755122

Experimental method

ELECTRON MICROSCOPY (2.81 Å)