Fig. 3: Structural basis of recognition of bemnifosbuvir and sofosbuvir by SARS-CoV-2 ExoN.
From: Mechanism of SARS-CoV-2 resistance to nucleotide analog-based antivirals
a Cryo-EM map and atomic model of SARS-CoV-2 ExoN E191A mutant in complex with T20P14-B RNA (referred to as ExoN•T20P14-B complex). b Cryo-EM map and atomic model of SARS-CoV-2 ExoN E191A mutant in complex with T20P14-S RNA (referred to as ExoN•T20P14-S complex) (tetrameric form). c ExoN active site conformation of the ExoN•T20P14-B complex. Metal coordination bonds are shown as gray dashed lines. +1BP, −1CP, Mg2+ ion, three catalytic carboxylate residues, and nsp14 α4-α5 loop are superimposed with their cryo-EM densities. d Superimposition of ExoN active site in the presence of T20P14-B or a standard RNA (PDB 7N0C). Root-mean-square deviation (RMSD) of the superimposition is indicated. The major shift of H268 upon the binding of T20P14-B is indicated. e ExoN active site conformation of the ExoN•T20P14-S complex (tetrameric form). +1SP, −1CP, Mg2+ ion, three catalytic carboxylate residues, and nsp14 α4-α5 loop are superimposed with their cryo-EM densities. The inactive and activated conformations of the α4-α5 loop are colored in orange and green, respectively. f Superimposition of ExoN active site in the presence of T20P14-S (tetrameric form) or a standard RNA (PDB ID 7N0D). For clarity, only the inactive conformation of the nsp14 α4-α5 loop in the ExoN•T20P14-S complex is shown. RMSD of the superimposition is indicated.
