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New York, December 22, 2024 — Scientists have announced a game-changing discovery in the fight against viral diseases, including COVID-19, Ebola, and Dengue. A pioneering team led by Thomas Tuschl at Rockefeller University has unveiled a new class of antiviral compounds targeting viral methyltransferases. This breakthrough could offer a novel strategy for treating both RNA and DNA viruses, potentially reshaping the landscape of antiviral therapies and preparing the world for future pandemics.
Since the introduction of Paxlovid in December 2021, which has proven highly effective in treating COVID-19, scientists have been concerned about the long-term efficacy of antivirals due to the possibility of drug resistance. As new variants of SARS-CoV-2 emerge and global health threats continue to evolve, the need for alternative therapies has become more pressing. The new research led by Tuschl offers a promising solution to this challenge.
A pivotal study from Tuschl’s laboratory highlights the potential of targeting a class of enzymes known as methyltransferases, which are critical for the replication of a wide range of viruses. Unlike most current antiviral treatments, such as Paxlovid, which target proteases—enzymes involved in protein breakdown—this new approach focuses on inhibiting enzymes that help viruses modify their RNA, making them more resilient against immune attacks.
“We’ve identified an entirely new target for antiviral development,” said Tuschl, a leading expert in RNA biology. “By targeting viral methyltransferases, we can tackle a mechanism that viruses rely on to thrive, without affecting human enzymes. This opens up exciting possibilities for broad-spectrum antiviral treatments.”
The study’s breakthrough is based on the discovery of small molecules that inhibit the viral cap methyltransferase enzyme NSP14, which plays a crucial role in stabilizing viral RNA. This enzyme is present in SARS-CoV-2, as well as a variety of other RNA viruses, including Ebola and Zika, and even some DNA viruses, such as Pox viruses. Tuschl’s team screened hundreds of thousands of compounds and identified several that showed promise in inhibiting this viral enzyme.
The compounds were further developed and tested in collaboration with other research teams, including those led by Charles M. Rice at Rockefeller University and the Center for Discovery and Innovation in New Jersey. Early tests on mice showed that the antiviral compounds were as effective as Paxlovid in treating COVID-19, with the added advantage of being effective even against viral mutations. Additionally, when combined with existing protease inhibitors, the compounds showed synergistic effects, making it virtually impossible for the virus to escape the treatment.
“This is a major step forward,” said Rice, a Nobel Prize-winning scientist. “Not only does it provide a new avenue for combating COVID-19, but it also lays the groundwork for future therapies against other viral diseases that have been difficult to treat.”
One of the most promising aspects of this discovery is its minimal side effects. Tuschl’s team notes that the compound selectively targets viral methyltransferases, leaving human enzymes unharmed. This specificity suggests that the new treatment could be safer than other antiviral drugs, which often come with significant side effects.
However, Tuschl cautioned that while the compound shows great promise, it is not yet ready for human clinical trials. “We still need to improve the stability and bioavailability of the compound, as well as optimize its pharmacological properties,” he explained. “This will require further collaboration with industry partners.”
Looking ahead, Tuschl and his team are expanding their research to explore the potential of this approach for other diseases, including respiratory syncytial virus (RSV), flaviviruses like Dengue and Zika, as well as emerging pathogens like mpox. The hope is that this breakthrough will offer a rapid and versatile weapon against a broad array of viral threats, providing a vital tool in preparing for future pandemics.
“This is a new opportunity to stay one step ahead of evolving viruses,” said Tuschl. “By targeting viral enzymes that are shared across different pathogens, we can develop therapies that are effective against a wide range of viruses, making the world more resilient to future health crises.”
The full study was published in Nature on December 11, 2024. As the research progresses, this new class of antiviral drugs could represent a major leap in global efforts to combat viral diseases and ensure more effective responses to future outbreaks.
For more information, read the full study: “Small-molecule inhibition of SARS-CoV-2 NSP14 RNA cap methyltransferase” by Cindy Meyer et al., DOI: 10.1038/s41586-024-08320-0.
