This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: A study co-led by a University of California, Riverside, biomedical scientist has identified new targets for coronavirus antiviral drugs, including treatments that may be less vulnerable to the rapid evolution of these viruses. The research, led by Joy Xiang at UC Riverside and Gene Yeo at UC San Diego, mapped previously unknown interactions across the SARS-CoV-2 genome between RNA and proteins involved in the virus's replication and regulation.
SARS-CoV-2 is the coronavirus that causes COVID-19. The team identified specific sites involving the RNA-dependent RNA polymerase (RdRp) and the nucleocapsid (N) protein and found that disrupting these interactions significantly reduced viral replication. The findings, published in Nature Communications, offer an early proof of concept for targeting the virus at critical points in its life cycle rather than focusing on rapidly changing features such as the virus's spike protein.
"SARS-CoV-2 evolves very quickly, so it's important to understand the really basic and essential machinery of the virus," said Xiang, an assistant professor of biomedical sciences in the UCR School of Medicine. "If we target something essential that the virus depends on to function and can't easily change, the virus is less likely to evolve away from it, which would lead to drug resistance." Current antiviral drugs already illustrate the value of targeting essential viral machinery. Remdesivir targets RdRp, the enzyme that copies the virus's RNA genome, while Paxlovid targets viral proteins involved in processing the long protein chains produced during infection.
Xiang and her collaborators used a technique known as enhanced cross-linking and immunoprecipitation, or eCLIP, to survey the viral genome and determine where viral proteins interact with RNA. Rather than examining only regions predicted in advance to be important, the approach allowed the researchers to map interactions across the genome and identify unexpected sites. One finding involved the N protein and a region at the beginning of the viral genome known as the 5′ untranslated region.
This region contains a complex RNA structure that is highly conserved among coronaviruses, but whose precise functions are not fully understood. The researchers found that its interaction with the N protein appears to regulate translation, the process by which viral RNA is used to make proteins. The researchers also identified a previously unknown interaction involving RdRp and the RNA encoding viral protein NSP3.
The finding suggests that viral RNA may play regulatory roles beyond simply serving as a template for producing proteins. "Viruses look simpler than humans at first glance, but there's a lot of underlying complexity to their molecular biology we're only just beginning to unravel," said Yeo, a professor of cellular and molecular medicine at UC San Diego. "Our findings suggest that viral RNA may have a more significant role in regulating fundamental cellular processes than we previously understood." Discover the latest in science, tech, and space with over 100,000 subscribers who rely on Phys.org for daily insights. d research that matter—daily or weekly.
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