Key result
Remdesivir monophosphate at the third primer position induces a translocation pause by increasing the binding affinity of Mg2+-PPi to the polymerase through a new hydrogen bond with K593.
Population
SARS-CoV-2 RNA-dependent RNA polymerase complexes
Comparison
Incorporation of remdesivir monophosphate (RMP) vs Incorporation of adenosine monophosphate (AMP)
Design
Preclinical
Authors
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No clinical practice changes warranted; leaves open translation of this polymerase mechanism to patient outcomes.
Molecular dynamics simulations reveal that remdesivir inhibits SARS-CoV-2 RNA polymerase by disrupting the hydrogen bond network necessary for translocation and causing steric hindrance.
Shi et al. (2022) studied SARS-CoV-2. Remdesivir monophosphate (RMP) vs. Adenosine monophosphate (AMP) was evaluated on Binding affinity and hydrogen bonding of Mg2+-PPi. Remdesivir monophosphate at the third primer position induces a translocation pause by increasing the binding affinity of Mg2+-PPi to the polymerase through a new hydrogen bond with K593.
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