Key result
The cryo-EM structure of the SARS-CoV-2 RNA-dependent RNA polymerase reveals that Remdesivir is incorporated into the first replicated base pair and terminates chain elongation.
Why the study?
SARS-CoV-2 replication requires viral RNA-dependent RNA polymerase, a direct target of remdesivir, but its structural basis was needed to provide insights into viral RNA replication and drug design.
The study provides the structural basis for how Remdesivir inhibits the SARS-CoV-2 RNA-dependent RNA polymerase by terminating chain elongation.
Elucidates Remdesivir's SARS-CoV-2 mechanism; leaves open refinement of polymerase inhibitors for clinical use.
The pandemic of Corona Virus Disease 2019 (COVID-19) caused by SARS-CoV-2 has become a global crisis. The replication of SARS-CoV-2 requires the viral RNA-dependent RNA polymerase (RdRp), a direct target of the antiviral drug, Remdesivir. Here we report the structure of the SARS-CoV-2 RdRp either in the apo form or in complex with a 50-base template-primer RNA and Remdesivir at a resolution range of 2.5-2.8 Å. The complex structure reveals that the partial double-stranded RNA template is inserted into the central channel of the RdRp where Remdesivir is incorporated into the first replicated base pair and terminates the chain elongation. Our structures provide critical insights into the working mechanism of viral RNA replication and a rational template for drug design to combat the viral infection.
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Yin et al. (2020) studied COVID-19 / SARS-CoV-2. Remdesivir was evaluated on Cryo-EM structure of SARS-CoV-2 RdRp complex. The cryo-EM structure of the SARS-CoV-2 RNA-dependent RNA polymerase reveals that Remdesivir is incorporated into the first replicated base pair and terminates chain elongation.
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