A promising strategy for development of broad-spectrum antiviral therapies involves promoting a strong immune response capable of stopping a number of viruses in their infectious tracks, according to researchers.
The body's first line of defense against foreign invaders is triggered by blocking the function of a specificidase in all cells. When challenged by several types of viruses in the study, the response dramatically lowered the replication of viral particles and the protection of mouse lungs from damage.
Scientists say the finding could change the approach to developing antiviral medications.
The saying is "one bug, one drug" when it comes to antiviral development, according to the co-senior author of the study.
One drug against multiple bugs is an ideal situation for a drug that stimulates the immune system.
There is a study in the journal.
The researchers were able to discover this discovery by using a technique to map the precise location of an RNA modification they were studying. The mapping led them to believe that the work of this enzyme is done in mammal hosts that the Viruses want to harm.
You can target the modification if you can detect it. In the beginning of the Pandemic, a lot of people, including our lab, were studyingRNA modifications in hosts andviruses. It turns out that the key to this is a hostRNA modification, which causes a host immune response.
Two viruses that can cause severe respiratory infections in infants and the elderly were among the Viruses tested against the immune response. The researchers said preliminary data from earlier studies in cell cultures suggested that the SARS-CoV-2 virus could be similarly controlled by blocking theidase.
m 5 C is what needs to be altered in order for the immune system to respond. It is one of roughly 170 known chemical modifications onRNA molecule that affect biological processes in a variety of ways.
Instead of targeting the modification, researchers were able to stop the function of the NSUN2idase, which is involved in that process. Suppressing NSUN2 using gene knockdown techniques and experimental agents led to robust production of type 1 interferon, one of the most potent fighters in the innate antiviral response.
A model virus that normally kills the host cells within 24 hours and replicates to a very high titer is almost completely shut down by blocking NSUN2.
It turns out that blocking NSUN2's function in cells exposesRNA snippets that are seen as foreign invaders whichtrigger the type 1 interferon production. The real threat is theviruses trying to cause infections.
The effects of blocking NSUN2 in mice were observed after the researchers verified this sequence of events.
We compared NSUN2 deficient mice with wild-type mice to find out how the viruses work. There was less pathology in the lung after we reduced NSUN2 and that correlated with enhanced type 1 interferon production.
We found that NSUN2 is a druggable target.
The researchers said that the next step was to develop a drug that would suppress NSUN2's function.
The work was co-authored by Li-Sheng Zhang. The founder of the drug-development company has filed a patent.
More information: Zhang, Yuexiu et al, 5-methylcytosine (m5C) RNA modification controls the innate immune response to virus infection by regulating type I interferons, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2123338119. doi.org/10.1073/pnas.2123338119 Journal information: Proceedings of the National Academy of Sciences
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