Trapping a non-cognate nucleotide upon initial binding for replication fidelity control in SARS-CoV-2 RNA dependent RNA polymerase.

The RNA dependent RNA polymerase (RdRp) in SARS-CoV-2 is a highly conserved enzyme responsible for viral genome replication/transcription. To understand how the viral RdRp achieves fidelity control during such processes, here we computationally investigate the natural non-cognate cognate nucleotide addition and selectivity during viral RdRp elongation. We focus on the nucleotide substrate initial binding (RdRp active site open) to the prechemical insertion (active site closed) of the RdRp.