Figure 1.

How does RDV work against SARS-CoV-2?

(Top) The viral polymerase (blue oval) uses RDV-TP as a substrate and incorporates RDV-MP (red) into the RNA primer strand (green bubbles) opposite UMP in the template (yellow/clear bubbles). A clash between the incorporated RDV-MP and S861 blocks translocation of the polymerase, which inhibits its ability to bind the next nucleoside triphosphate (N) at position i + 4. (Bottom) Inhibition at position i + 3 is not complete, the primer is eventually extended and is later used as a template (now green). Here, RDV-MP clashes with A558, which reduces binding of UTP(U). V557L is a mutation in the polymerase that can in part neutralize this effect. This mutation is associated with low-level resistance to RDV in MHV. Adapted from Ref. [27^••].