Due to the completeness of the entire replication machine both in terms of amino acids and of the structural chains making up the entire viral RNA replication complex, which requires the presence of Nsp12, Nsp7, and Nsp8, the cryo-EM model with the PDB ID 7ED5 was selected as a reference structure (Figure 1 ). Here, the triphosphate form of the original AT-527 ligand in the catalytic site of RdRp is still not incorporated in the RNA strand, and is ready for the hydrolysis reaction of pyrophosphate groups (AT9) [44 (link)].
The original ligand was extracted and the apo-form of the target was optimized by using the Protein Preparation Wizard tool of Maestro suite (Schrödinger Release 21.4) [45 (link)] and OPLS_2005 as force field [46 (link)] in order to delete complexed water molecules, adding hydrogen atoms, correcting the connectivity, and generating the exact protonation states at pH 7.4. Missing side chains and loops were built using Prime [47 (link)].
The original ligand was extracted and the apo-form of the target was optimized by using the Protein Preparation Wizard tool of Maestro suite (Schrödinger Release 21.4) [45 (link)] and OPLS_2005 as force field [46 (link)] in order to delete complexed water molecules, adding hydrogen atoms, correcting the connectivity, and generating the exact protonation states at pH 7.4. Missing side chains and loops were built using Prime [47 (link)].
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