Structural basis of mismatch recognition by a SARS-CoV-2 proofreading enzyme

Abstract

A proofreader in SARS-CoV-2 Although vaccines provide protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there remains a need for antivirals to treat COVID-19. Nucleotide analog drugs such as remdesivir, which target the viral RNA polymerase, have potential but are compromised by exoribonuclease (ExoN) activity that removes incorrect nucleotides from newly synthesized RNA. Liu et al . determined the structure of the complex that harbors the ExoN activity (nsp10–nsp-14) bound to a mimic of RNA that has incorporated an incorrect nucleotide. The structure shows how the RNA is recognized and suggests how ExoN specifically removes mismatched nucleotides. It also provides clues for designing nucleotide analogs that may evade excision. —VV