The above observations altogether indicate that the "template-dependent inhibition mechanism" is not exerted by directly impairing the NTP incorporation at the active site. In this regard, the inhibition could be applied by the second scenario, where the translocation is hampered and the NTP incorporation is inhibited. To examine the propensity of translocation when Remdesivir moves from +2 to +1 site along the template strand, we first evaluated the influence of Remdesivir on the stability of both the pre-and post-translocation states by performing MD simulations for SARS-CoV-2 RdRp with Remdesivir at +1 site and +2 site in the post-translocation state and pretranslocation states, respectively (see SI Section 1.2 and 2.2 for details). SARS-CoV-2 RdRp with wildtype double-stranded RNA (dsRNA) in both states have also been examined for comparison (see SI Section 1.1 and 2.1 for details). The hydrogen bonding probability between the template and nascent strands was computed to estimate the thermal stability of both states. Our results have demonstrated that when Remdesivir is present in both states, the base pairs at -1, -2 and -3 site are well maintained (hydrogen bonding probabilities > 85%), resembling the scenario observed for the RdRp with wildtype dsRNA (Fig. ). This result has suggested that the translocation of Remdesivir from +2 to +1 site is thermodynamically allowed.