Nat Commun: Redsiwell overturned? Why can't it completely block coronavirus infection?

January 18, 2021 // -- Redsyvir is the first drug in Europe and the United States to be conditionally approved to fight COVID-19, which inhibits SARS-CoV-2 in human cells by blocking viral replication machines called RNA polymerases In a recent study published in the international journal Nature Communications, scientists from the Planck Institute and others used research to reveal the molecular mechanisms of viral polymerases during redsivir's intervention in virus replication, and why Redsyvir could not completely inhibit the replication of SARS-CoV-2.
researcher Patrick Cramer said: 'After complex studies, we have come to the simple conclusion that when Redsyvir does interfere with the function of the virus's RNA polymerase during its function, but only after a period of time;
When COVID-19 began to become popular, the researchers clarified the mechanisms and methods of the coronavirus replicator RNA genome, which is a difficult task for pathogens because its genome consists of about 30,000 basic RNA components, which makes it particularly long.
Photo Source: Hauke Hillen, Goran Kokic, and Patrick Cramer/Max Planck Institute for Biophysical Chemistry In a joint study, researchers developed special RNA molecules for structural and functional studies, and Redsyvir's structure is similar to the basic components of RNA, so that the virus's RNA polymerase is misled and can integrate the drug into an extending chain of RNA.
When Redsyvir was integrated into the virus's genome, the researchers analyzed the function of the polymerase-RNA complex using bio-chemical methods and cryogenic electroscopy techniques, and found that when Redsyvir was added to the RNA chain, the virus replication process was precisely suspended when three additional basic components were added.
This polymerase does not allow the loading of a fourth polymerase, which is caused by two atoms in the Redsivir structure being hooked up at a specific location of the polymerase;
Understanding the mechanism of Redsyvir's role may provide scientists with new opportunities to effectively address the disease and spread of the virus, the researchers said. To improve the development of Redsyvir and its mechanisms of action, we hope to be able to find a variety of new compounds to block the replication of the virus machine, the vaccine strategy currently being developed is critical to controlling the epidemic of disease, and we also need to develop effective drugs to slow the progression and spread of COVID-19 disease in populations.
() Original source: Kokic, G., Hillen, H.S., Tegunov, D. et al. Mechanism of SARS-CoV-2 polymerase stalling by remdesivir. Nat Commun 12, 279 (2021). doi：10.1038/s41467-020-20542-0