Exactly how virus clones is a complex puzzle with many missing puzzle pieces. And in the pandemic era, solving it has become an urgent problem.
Finding the details of the basic replication activities that make one virus into thousands of other could give scientists a major step forward in discovering new drugs that might be possible. prevents SARS-CoV-2 and prevents its trace infection.
In a new study published above UMBRELLAThe Rockefeller scientists present an important piece of the puzzle: an atomic-resolution look at the SARS-CoV-2 replication system. “We now have an additional structural pattern that could be really helpful for drug developers trying to find new compounds that can break into,”; said Elizabeth Campbell, associate professor of research at Rockefeller. this molecular machine and shut it down. “
Like many other viruses, the coronavirus replicates its genetic material with the help of a complex enzyme as its name implies: RNA-dependent RNA polymerase, or RdRp. Because it is absolutely essential for viral replication, this machine is believed to be a promising target for antiviral drugs. In fact, a number of existing antivirals, as well as a number of new candidates are being investigated specifically for COVID-19 that works on RdRp – including remdesivir, which is currently being used in some country for the treatment of serious cases.
These antiviral drugs try to creep into the nooks and crannies of the giant RdRp molecule, like a blockage inside its gear, shutting down the machine. To achieve this, a compound needs to be particularly precise – meaning that scientists trying to design a successful compound need the most detailed picture of the RdRp they can get.
Even more complicated is the fact that RdRp does not work alone. It combines with several other proteins, including another important enzyme called helicase, which in its own right is a promising target for the discovery of the drug COVID-19. James Chen, a postdoctoral associate at Seth Darst’s lab and one of the study’s first authors, said “the tight gene cluster of RdRp and these binding proteins could be” the enzyme that looks like just like outside the lab and in the natural environment, inside an infected cell.
Using a powerful imaging technique called cryoelectron microscopy, Darst and Campbell’s team, and their collaborators in Brian Chait and Tarun Kapoor’s labs, were able to accurately render. What does this multi-part machine look like. The good news: Even when they form a complex, the compartments of the RdRp or helicase do not change shape, so molecules designed to inhibit these enzymes individually are still able to function. on duo. Furthermore, the picture shows several previously unknown locations in the machine that could be vulnerable to drug attacks – including a point at the interface between two enzymes, a joint potentially broken by a molecule. intervention.
Cracking coronavirus and more
The new discoveries can improve human health in a number of ways. In the case of COVID-19, as scientists around the world are racing to find antiviral molecules, the new data could dramatically speed up their work. In particular, the unprecedented resolution team that created the 3-D map of the RdRp-helicase complex will support computational studies in which researchers explore the function of “virtual” drug candidates. , based on their knowledge of the chemical structure of molecules.
“When a person is looking for molecules that can get into a particular bonded bag, there’s a detailed picture of the picture,” says Brandon Malone, a PhD student at Rockefeller and co-author of the study. The shape of that bag will greatly improve the computational connection accuracy.
In addition to COVID-19, the new discovery could also help scientists narrow their idea of how exactly two enzymes read and replicate genetic material in all so-called RNA viruses, a large group of Pathogens include everything from coronavirus to dengue fever, Ebola, and the common cold.
“Now, we can not only propose models for virus replication, but actually test those models.” Chen said.
Amidst the fever bought the drug COVID-19, a case for helicase bacteria
James Chen et al. The structural basis for helicase-polymerase coupling in the transcription-transcription complex SARS-CoV-2, UMBRELLA (Year 2020). DOI: 10.1016 / j.cell.2020.07.033
Provided by Rockefeller University
Quote: Unseen image of the coronavirus replicator (2020, August 10) retrieved August 11, 2020 from https://phys.org/news/2020-08-osystem-before-seen-image -coronavirus-machine. html
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