The USA A detailed map of the machine controlling CoV’s multiplication will help researchers accelerate the development of a special remedy.
The bond between RdRp and helicase is indicated in blue. Photo: Sci Tech Daily.
In the new study published in the Cell journal, the Rockefeller scientists provided a snapshot of the CoV replication system at the atomic level. “We now have more structural archetypes that can help pharmaceutical companies find compounds to block nCoV,” says Elizabeth Campbell, associate professor at Rockefeller University.
Like many other viruses, nCoV copies genetic material with the help of a complex enzyme as its name implies, RNA polymerase dependent RNA or RdRp. Because it is essential for viruses to multiply, this machine is a potential target for antiviral drugs. In fact, a number of current antiviral drugs as well as some new special drugs for Covid-19 work based on RdRp, including remdesivir. Remdesivir is being used in many countries to treat severe illness.
These antiviral drugs try to creep into the nooks and crannies of the giant RdRp molecule like an obstacle that clogs the machine, causing the machine to shut down. To do this, the compound needs to be extremely precise. Researchers are looking for a way to design a successful compound that requires the best possible detailed photographs of RdRp. The problem is compounded by the fact that RdRp does not work alone but combines with several other proteins, including the enzyme helicase, another promising target for the preparation of the therapeutic drug Covid-19.
Using a imaging technique called cryoelectron microscopy, the team was able to show what nCoV’s multi-part replication machine looks like. Even when forming a complex complex, the flaws of the RdRp or helicase do not change shape, so the molecule designed to inhibit these enzymes is effective against both. The snapshot also reveals many previously unknown areas in the machine and is susceptible to attack by drugs, including a point in the surface between the two enzymes.
While scientists around the world are in a hurry to look for molecules that are resistant to CoV, the new data could significantly speed up their research. In particular, the resolution of the 3D map of the RdRp-helicase combination created by Campbell et al. Will help in computer studies of the drug’s function.