Coronaviruses duplicate their RNA genome using a specialized polymerase

SARS-CoV-2 RNA-directed RNA polymerase (nsp12) with nsp7 and nsp8, and a short duplex of RNA with a template strand and a product strand. Nsp7 and 8 are removed on the right to show the interaction with RNA. Download high quality TIFF image

Some viruses, including poliovirus, rhinovirus , and coronaviruses, don't bother with DNA at all. They transmit their genetic information as a strand of RNA that can be used as a messenger RNA to build proteins as soon as the virus infects a cell. One of the tricks, however, is that these viruses need a special polymerase that goes against the standard DNA-to-RNA-to-protein information flow. This polymerase makes a new RNA strand using RNA, not DNA, as the template. So, the virus simply needs to encode this polymerase in its RNA genome. Then, the polymerase is made by cellular ribosomes soon after infection and it starts replicating the viral RNA to make new viruses.

Under the Microscope

7bzf, Amazingly, only a few months after SARS-CoV-2 was discovered, researchers are revealing the structure its RNA-dependent RNA polymerase and exploring its interactions with RNA. Cryoelectron microscopy is being used to determine the structures of the polymerase and its helper proteins, along with small pieces of RNA. A few of the first structures can be found in PDB entries 6yyt (shown here), 7c2k 7bv2 , and 6x2g . These structures include the polymerase (also known as nsp12 for "non-structural protein 12") along with two other viral proteins, nsp7 and nsp8, that help the polymerase stay on track and copy long portions of the RNA chain.

Perfect Target

Since our own cells don't make RNA from RNA, this polymerase is an attractive target for antivirals. New drugs usually take a long time to perfect since they have to be evaluated for effectiveness and safety, but investigational polymerase-targeting agents like remdesivir are being repurposed in the fight against COVID19. Remdesivir was developed to fight hepatitis and Ebola, but wasn't very effective. It is currently approved for emergency use against SARS-CoV-2.