In response to the COVID-19 pandemic, researchers examined structural components of SARS-CoV-2 (the coronavirus responsible for COVID-19) to identify avenues for effective treatment. Now, researchers are comparing what we know about different coronaviruses to explore whether therapeutics may be effective across this virus family.
“A lot of the available structural data for coronaviruses focuses on SARS-CoV-2, but that’s a sliver of the diversity of coronaviruses out there,” says Robert Kirchdoerfer, an assistant professor in the Department of Biochemistry. “SARS-CoV-2 is a beta-coronavirus. There are also alpha-, delta-, and gamma-coronaviruses, which we have far less information about.”
Earlier this year, the Kirchdoerfer Lab published high-resolution images of the RNA polymerase (a protein complex key to RNA replication) in an alpha-coronaviruses. Comparing their images to structural data of SARS-CoV-2 revealed that the orientation and function of the RNA polymerase complexes is conserved between alpha- and beta-coronaviruses.
In a new study published in the Journal of Biological Chemistry, the researchers determined the RNA polymerase structure of infectious bronchitis virus, a gamma-coronavirus with active sites and binding sites similar to SARS-CoV-2.
The researchers also examined a protein loop essential to assembly of the RNA polymerase in infectious bronchitis virus. Their findings indicate that while the loop is present in alpha-, beta-, and gamma-coronaviruses, its specific interactions differ among the coronavirus types. As a result, a drug that potentially inhibits the loop’s interactions in one type of coronavirus may not inhibit such an interactions in another.
“Knowing about differences among coronaviruses gives us important information about what we should be studying if a new coronavirus emerges so that we can be more prepared for the next pandemic,” says Kirchdoerfer.
Written by Renata Solan.