Mechanism of SARS-CoV-2 polymerase stalling by remdesivir
2021
Max Planck Institute for Biophysical Chemistry, Goettingen, Germany(1)
Universität Würzburg, Wuerzburg, Germany(2)
Universität Würzburg, Wuerzburg, Germany(2)
Biochemical methods along with cryo-electron microscopy have revealed why the drug remdesivir is only moderately effective against the proliferation of SARS-CoV-2. RNA polymerase complexes were analysed for this purpose. Remdesivir interferes with viral RNA polymerase by being incorporated into the RNA chain due to its structural similarity to the RNA nucleotides. When incorporated, it becomes entangled within the polymerase. Three more nucleotides are added, but a fourth is not, thereby stalling the polymerase. However, the drug does not stop viral RNA polymerase completely as proofreading can occur and the enzyme can continue the polymerization. Now that the mechanism is known, substances and their effects can be optimized to effectively combat coronavirus infections.
Mechanism of SARS-CoV-2 polymerase stalling by remdesivir
Patrick Cramer(1), Claudia Höbartner(2)
Added on: 01-29-2021
[1] https://www.nature.com/articles/s41467-020-20542-0[2] https://www.bionity.com/en/news/1169427/why-remdesivir-does-not-fully-stop-the-coronavirus.html