Figure 3.

Mechanism of activation through O3′ deprotonation inside RdRp

(A) Scheme depicting the activation mechanism used by SARS-CoV-2 RdRp.

(B) Free-energy profile as a function of the proton transfer coordinate (d3-d4), obtained for the proton transfer reaction between the O3′ of the just-incorporated nucleotide and the γ phosphate group of the newly formed PPi.

(C) Transition state (TS) where the H3′ proton belonging to O3′ atom of nucleotide “i” is halfway to being transferred to γ phosphate group of PPi. Reaction coordinate (RC) consisted of the distances between O3′ or Oγ atoms to the H atom to be transferred, displayed as d3 and d4, respectively.