A new step in the development of new corona therapeutics, what exactly is a 'frameshift' inhibitor?



Since there is no cure for the new coronavirus infection (COVID-19), it is considered essential to spread vaccination to control the epidemic. Meanwhile, Pfizer and other pharmaceutical companies are also working on the development of COVID-19 treatments. In a new study, a method was announced that does not adversely affect the human body and inhibits the replication of the new coronavirus (SARS-CoV-2) alone. This method is expected to pave the way for new therapeutic agents.

Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome | Science
https://science.sciencemag.org/content/early/2021/05/12/science.abf3546



The Achilles heel of the Coronavirus | ETH Zurich
https://ethz.ch/en/news-and-events/eth-news/news/2021/05/the-achilles-heel-of-the-coronavirus.html

The process of 'synthesizing proteins in the RNA genome' is essential for the process by which a virus spreads from cell to cell and from person to person. In this process, the virus uses the ribosome , which is the replication device of the cells it has infected, to synthesize its own protein.

When not infected with a virus, the ribosome reads the three-letter code of RNA that defines the amino acids required for protein growth. Ribosomes usually do not misread one or two of these three letters. A code shift is called a 'frameshift' and when it occurs in humans it causes the production of dysfunctional cellular proteins.

However, certain viruses, such as coronavirus and HIV, use frameshifts to regulate viral protein levels. SARS-CoV-2 is no exception, and frameshifting is essential for its replication.

This means that if a compound that inhibits the frameshift that 'almost does not occur in human cells but is essential in SARS-CoV-2' is developed, it will become a therapeutic drug for COVID-19. It means that it can be.

A research team from the ETH Zurich, the University of Bern, the University of Lausanne, and the University of Cork focused on the above points and revealed for the first time what kind of interaction occurs between the RNA genome of SARS-CoV-2 and the ribosome. I made it. 'The results of this study on SARS-CoV-2 should also help us understand the mechanism of frame shifts in other RNA viruses,' said Nenad Ban, a professor of molecular biology at the ETH Zurich. I have commented.

Below is how the ribosome is reading the RNA information for SARS-CoV-2. The brown part is the ribosome, the yellow string is the RNA of SARS-CoV-2 virus, and a frameshift occurs when reading the differently colored part on the yellow string.

SARS-CoV-2 --YouTube


Previous studies have shown that some compounds can inhibit the frame shift of SARS-CoV-2, but this study shows how compounds are at SARS-CoV-2 levels in infected cells. Information was also mentioned as to whether it would affect the disease. Specifically, as a result of using two kinds of compounds in the experiment, both of them did not adversely affect the cells and the replication of the virus was suppressed 3 to 4 times. However, while one of the two species suppressed replication by inhibiting frameshifting, the other is said to have involved a different mechanism.

These compounds are not expected to be effective enough to be used as therapeutic agents at the time of writing the article. However, this study is believed to have paved the way for the development of therapeutic agents that take advantage of frameshift inhibition. It may also be useful in treating infectious diseases other than coronavirus.

in Science,   Video, Posted by darkhorse_log