No parentheses needed, the virus is merely smarter

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We have summarized the mechanism of remdesivir-induced RdRp stalling in a molecular animation (Supplementary Movie 1). The remdesivir-stalled state is observed in our structure 2. In this structure, the RNA product 3ʹ-nucleotide is buried in the active center and is base-paired with the RNA template strand (Fig. 3a, b). This may explain why the RNA 3ʹ-end may at least partially escape proofreading by the viral exonuclease nsp1429,30. Nevertheless, some proofreading can occur and this renders remdesivir less efficient19, indicating that the viral exonuclease can remove several nucleotides from the base-paired RNA 3ʹ-end. Such removal of several RNA nucleotides may require RNA backtracking along the RdRp, and this may be induced by the viral helicase nsp1331.

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