Dr Merja Joensuu (R) and a colleague, look at cells through a microscope.
Photo Credit: The University of Queensland
Scientific Frontline: Extended "At a Glance" Summary: NMT1 Antiviral Pathway Breakthrough
The Core Concept: A novel antiviral treatment strategy that inhibits the human enzyme N-myristoyltransferase 1 (NMT1) to prevent viruses from successfully assembling and replicating inside host cells.
Key Distinction/Mechanism: Traditional antivirals target the pathogen directly, which frequently leads to viral mutation and drug resistance. This new approach instead disrupts the human cellular pathway that viruses hijack during reproduction. By altering host cell function, the targeted pathway forces the cell to produce defective, less-effective viral particles, granting the immune system critical time to clear the infection.
Major Frameworks/Components:
- Enzymatic Target: The therapy utilizes a compound—currently undergoing clinical trials as a cancer treatment—to inhibit NMT1, an enzyme responsible for directing protein location and function within cells.
- Viral Assembly Disruption: By altering spatial organization and cellular function, the drug ensures that new viral copies are constructed incorrectly.
- Broad-Spectrum Efficacy: Laboratory cell culture tests demonstrated significant efficacy against diverse infectious agents, including SARS-CoV-2, respiratory syncytial virus (RSV), and vesicular stomatitis virus.
- Rapid Pathogen Reduction: Researchers observed viral infection levels drop by approximately 50 percent after one day, and up to 90 percent after two days.
Branch of Science: Virology, Biochemistry, Pharmacology, and Infectious Diseases.
Future Application: The compound shows high potential as a broad-spectrum antiviral therapeutic. It could eventually be formulated as a nasal spray or inhaler for respiratory conditions, with broad applicability against high-mortality viruses with long incubation periods, such as Ebola and hantavirus.
Why It Matters: By targeting the host cell infrastructure instead of the virus itself, this methodology circumvents the severe global health challenge of viral drug resistance, offering a highly adaptable framework to neutralize multiple lethal infectious diseases simultaneously.
An unexpected observation by a University of Queensland researcher could lead to a new treatment for deadly infectious diseases, including COVID-19, pneumonia in infants and children, or viral infections caused by Ebola and hantavirus.
University of Queensland neuroscientist and biochemist Dr. Merja Joensuu said the idea came while she was working on unrelated research.
“We were studying how certain processes work inside the human brain when I noticed a disruption in a pathway that numerous human viruses rely on to spread from one cell to the next,” said Dr. Joensuu of UQ’s Australian Institute for Bioengineering and Nanotechnology. “That was the lightbulb moment. We realized that if we interfere with that pathway, we might be able to stop viruses from forming properly.”
With her collaborator, Professor Giuseppe Balistreri of the University of Helsinki, the research team searched for a compound that could inhibit this pathway and found one currently being trialed as a cancer treatment. The human enzyme N-myristoyltransferase 1 (NMT1), which helps direct where proteins are located and how they function within human cells, was the compound’s target.
“Viruses can’t reproduce on their own, so they hijack human cells to make new copies,” Professor Balistreri said. “This drug disrupts how the cell functions, causing new viruses to be assembled incorrectly. The virus doesn’t know this and keeps making and releasing less effective versions of itself, which would give the immune system time to clean up the infection.”
In laboratory studies, the researchers tested the drug against a range of viruses in cell cultures, including SARS-CoV-2 (which causes COVID-19); respiratory syncytial virus, a major cause of pneumonia in infants; and vesicular stomatitis virus, which causes disease in cattle, horses, and occasionally humans. They found that infection levels dropped by about half after one day and by up to 90 percent after two days.
“The reduction is quite striking,” Dr. Joensuu said. “The study also suggests this strategy could potentially work on viruses with high mortality rates and long incubation times, like Ebola and hantavirus. All viruses rely on exploiting host cell processes to replicate and spread. Because we are interfering with the host cell instead of directly targeting the virus, there is less chance of it mutating and building resistance to the drug.”
Researchers emphasized that the drug is not yet approved for this use, with further studies needed to confirm safety and effectiveness, but Dr. Joensuu said it showed a lot of promise.
“You can imagine that this could be a very effective antiviral—for example, in treating respiratory conditions—used in the form of a nasal spray or an inhaler,” she said.
Funding: This research was supported by the facilities and staff at the Centre for Microscopy and Microanalysis and the Queensland Node of Metabolomics and Proteomics Australia, both of which are housed at the AIBN and funded the Australian Government’s National Collaborative Research Infrastructure Strategy (NCRIS).
Published in journal: Nature Communications
Authors: Saber H. Saber, Nyakuoy Yak, Konstantin Dolski, Sanna Mäki, Lev Levanov, Levina A. Willenbrink, Julian D. J. Sng, Mohammed R. Shaker, Sean D. Morrison, Huiwen Zheng, Selin Pars, Giovanni Pietrogrande, Yih Tyng Bong, Tania Vane-Tempest, Teemu Smura, Tomas Strandin, Ravi Ojha, Ravi Kant, Janika Ruuska, Francesco Topi, Diana Vaskiv, Lauri Kareinen, Tobias Binder, Siyuan Lu, Matthias Floetenmeyer, Bahaa Al-mhanawi, Yanshan Zhu, Tarja Sironen, Gert Hoy Talbo, Kirsty R. Short, Wouter W. Kallemeijn, Roberto Solari, Jessica Mar, Edward W. Tate, Ashley J. van Waardenberg, Olli Vapalahti, Ernst Wolvetang, Giuseppe Balistreri, and Merja Joensuu
Source/Credit: University of Queensland
Edited by: Scientific Frontline
Reference Number: vi072926_01
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