Researchers at the University of California San Diego School of Medicine and the University of

New Coronavirus Drug Targets Identified by UC San Diego and UC Riverside Researchers

Researchers at the University of California San Diego School of Medicine and the University of California, Riverside School of Medicine have identified new potential targets for antiviral treatments against coronaviruses, including SARS-CoV-2. Published in the journal Nature Communications, the study maps previously unknown interactions between the RNA genome of the virus and proteins that drive replication and regulation, according to News-Medical.

The team found specific RNA binding sites for three essential viral proteins: the primase cofactor NSP8, the RNA-dependent RNA polymerase NSP12, and the nucleocapsid protein N. Disrupting these interactions significantly reduced viral replication in both animal cells and human lung cells. UA.News notes that the researchers utilized a technique called enhanced cross-linking and immunoprecipitation, or eCLIP, to survey the entire viral genome rather than focusing only on previously predicted regions.

Mapping RNA and Protein Interactions Across The Viral Genome

The eCLIP approach revealed unexpected sites where viral proteins interact with RNA across the entire genome. One key finding involved the N protein and a region at the start of the viral genome known as the 5’ untranslated region. UA.News reports that this complex RNA structure is present in many coronaviruses and its interaction with the N protein appears to regulate translation, the core cellular process that builds proteins from RNA instructions.

The researchers also uncovered an interaction between NSP12 and the RNA encoding viral protein NSP3. This discovery suggests that viral RNA performs active regulatory functions beyond serving merely as a template for protein production. Senior study author Gene Yeo, director of the Center for RNA Technologies and Therapeutics at UC San Diego School of Medicine, stated that viral biology possesses an underlying complexity that researchers are only beginning to understand.

Blocking Viral Replication With Locked Nucleic Acids

To test whether these newly identified interaction sites could be exploited therapeutically, the team applied locked nucleic acids, which are short, modified sequences designed to bind specific RNA regions and block protein interactions. Blocking these sites successfully reduced viral replication in animal and human lung cells. Joy Xiang, assistant professor of biomedical sciences at the UCR School of Medicine, explained that targeting core viral machinery that the pathogen cannot easily change lowers the likelihood of drug resistance developing.

Frequently Asked Questions

What specific technique did the researchers use to map the viral genome?

The research team used enhanced cross-linking and immunoprecipitation, known as eCLIP, which allowed them to survey protein-RNA interactions across the entire SARS-CoV-2 genome rather than restricting their analysis to previously predicted regions, according to News-Medical.

Which viral proteins were found to have specific RNA binding sites?

The study identified specific RNA binding sites for three proteins: the primase cofactor NSP8, the RNA-dependent RNA polymerase NSP12, and the nucleocapsid protein N.

How did the research team test the function of the identified RNA regions?

The researchers tested the regions by applying locked nucleic acids, which are short, modified nucleic acid sequences that bind to specific RNA fragments and prevent them from interacting with viral proteins.

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