Coronavirus Vulnerability Found: Blocking tRNA-Modifying Enzymes Could Halt Viral Spread
Researchers at Pompeu Fabra University (UPF) in Barcelona, Spain, have identified a key mechanism used by coronaviruses to hijack human cells and accelerate their own replication. The discovery, published in Nature Communications on February 19, 2026, points to a potential therapeutic target: enzymes that modify transfer RNAs (tRNAs). Blocking these enzymes could significantly curb viral protein production and offer a broad-spectrum antiviral strategy against coronaviruses, including those responsible for SARS, MERS, and COVID-19.
How Coronaviruses Reprogram Cells
Coronaviruses don’t simply utilize the machinery of the cells they infect; they actively modify it to create optimal conditions for producing viral proteins and spreading more rapidly. The UPF study reveals that viral infection triggers a stress response within cells, leading to chemical alterations in tRNAs. These alterations reshape the cellular machinery, prioritizing the production of proteins needed to combat stress – and, crucially, also benefiting the virus.
“Interestingly, coronaviruses need tRNAs that are in low concentrations in cells,” explains Elena Muscolino, first author of the study and a postdoctoral researcher in the Molecular Virology group at UPF [1]. “we asked ourselves how a virus can spread so quickly within a cell where the tRNAs it needs to develop its viral proteins are not abundant.”
tRNA Modification: A Viral Advantage
The research demonstrates that the stress-induced modifications to tRNAs allow coronaviruses to accelerate protein production without needing to create new cellular machinery. Instead, they alter the existing machinery to their advantage. This is because the same tRNAs required for the cell’s stress response are also needed for the virus to manufacture its proteins.
“In order to manufacture stress response proteins, the same tRNAs that coronaviruses need to manufacture their viral proteins are needed,” explains Mireia Puig, also an author of the work [4].
A Promising Therapeutic Target
The study found that the tRNA modification process occurs in both SARS-CoV-2, the virus responsible for COVID-19, and HCoV-OC43, a coronavirus that typically causes mild cold-like symptoms. This suggests that tRNA modification may be a common strategy employed by various coronaviruses.
Importantly, blocking the activity of the tRNA-modifying enzymes significantly reduced viral protein production in laboratory settings. “The tRNA-modifying enzyme is a promising candidate for developing broad-spectrum antiviral drugs capable of curbing the spread of coronaviruses,” says Juana Díez, director of the Molecular Virology Research Group at UPF [3]. “A drug of this type would allow us to contain the infections caused by new coronaviruses from their initial phases and prevent their rapid expansion, and new pandemics.”
The Urgent Need for Broad-Spectrum Antivirals
The research underscores the critical need for broad-spectrum antiviral drugs. “At present, we do not have any broad-spectrum antiviral drugs that are effective against coronaviruses,” Díez emphasizes. “So when a new coronavirus emerges, a scenario considered highly likely among the scientific community, we will be in the same position as at the end of 2019, when we did not have the drugs to control the spread of the virus.”
The UPF study was a collaborative effort involving researchers from the University of Glasgow, the Institute for Integrative Systems Biology in Valencia, and the Autonomous University of Barcelona.
Citation: Muscolino, E. Et al. Coronaviruses reprogram the tRNA epitranscriptome to favor viral protein expression. Nature Communications (2026). DOI: 10.1038/s41467-026-69700-w