We noticed that a previous study based on the structural modeling has suggested that the 1'-cyano group of Remdesivr at +1 site would clash with the backbone of the protein residue A558 and thereby destabilize the base pairing between UTP and Remdesivir . In our simulations, we indeed observed that A558 would move away from the 1'-cyano group of Remdesivir (Fig. ). Specifically, the distance between the backbone oxygen atom of A558 and the C1' atom of Remdesivir is 6.78Å±0.14Å, obviously larger than that between A558 and adenosine (4.7Å±0.23Å). However, such conformational changes seldom perturb the base pairing stability, as the hydrogen bonding probability of UTP:Remdesivir (>90%) is similar to that of UTP:A pair (Fig. ). Therefore, the static structural model alone is insufficient to examine the effect of 1'-cyano group of Remdesivir on the pre-catalytic conformation, and our simulations have demonstrated that the base pairing is well formed even though Remdesivir repels A558 away.