Key result
Remdesivir binds SARS-CoV-2 RNA polymerase more strongly than ATP in molecular dynamics simulations.
Why the study?
COVID-19 emerged as a deadly pandemic calling for new treatments, and understanding the inhibition mechanism of remdesivir to SARS-CoV-2 RNA-dependent RNA polymerase was needed.
Population
SARS-CoV-2 RNA-dependent RNA polymerase homology model
Comparison
Remdesivir vs natural substrate ATP
Design
Molecular dynamics simulations and free energy perturbation study
Authors
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Remdesivir's simulated binding advantage warrants no clinical change yet; leaves open mechanistic confirmation in trials.
Effect estimate: -2.80 kcal/mol
Molecular dynamics simulations suggest remdesivir binds significantly stronger to SARS-CoV-2 RdRp than ATP, supporting its potential role as an RNA-chain terminator.
Zhang et al. (2020) studied COVID-19. Remdesivir vs. ATP was evaluated on Relative binding free energy (-2.80 kcal/mol). Molecular dynamics simulations showed remdesivir binds much stronger to SARS-CoV-2 RNA-dependent RNA polymerase than ATP, with a relative binding free energy of -2.80 ± 0.84 kcal/mol.
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