Novel, potential target for broad-spectrum antiviral therapies identified

PTI, Oct 14, 2022, 11:52 AM IST

Representative Image (Source: Pinterest)

Scientists have found a new way to stop a number of viruses in their infectious tracks, identified a promising strategy for developing broad-spectrum antiviral therapies.

Scientists from the Ohio State University, US, conducted experiments in cell cultures and mice and found that blocking a specific enzyme present in all cells from functioning triggered a powerful innate immune response, the body’s first line of defence against any foreign invader.

This response, according to the study, when challenged by several types of viruses, dramatically lowered the replication of viral particles and protected mouse lungs from damage.

“Typically, in antiviral development, the saying is, one bug, one drug’, said Jianrong Li, from the Ohio State University, and co-senior author of the study published in the journal Proceedings of the National Academy of Sciences.

“A drug that can stimulate the immune system to have broad antiviral activities would be very attractive — one drug against multiple bugs would be an ideal situation,” Li said.

The discovery was enabled in part by a technique the researchers used to map the precise location of an RNA modification they were studying, and to see which enzyme made the modification.

The mapping led them to determine that this enzyme’s work happens not in viruses, but in mammal hosts that viruses want to infect.

“It turns out the key here is not a viral RNA modification, but a host RNA modification, and it triggers a host immune response,” said another co-senior author Chuan He, University of Chicago.

The RNA modification itself, known as cytosine-5 methylation, or m5C, is actually what needs to be altered to trigger the immune system response.

It is one of roughly 170 known chemical modifications on RNA molecules in living organisms that affect biological processes in a variety of ways.

In lieu of targeting the modification itself, researchers were able to inhibit the function of a key enzyme in that process, called NSUN2, to stop the RNA change.

They found that blocking NSUN2’s function in cells exposes RNA snippets that, despite belonging to the host, are seen as foreign invaders, which triggers the type 1 interferon production, one of the most potent fighters in the innate antiviral response.

Once available at this high level, the protein will stop the real threat: viruses trying to cause infection.

Amazingly, blockage of NSUN2 almost completely shuts down the replication of vesicular stomatitis virus, a model virus that normally kills the host cells within 24 hours and replicates to a very high titer, and strongly inhibits both RNA and DNA viruses, said study co-first author Yuexiu Zhang, a PhD student in Li’s lab.

The researchers verified this sequence of events during experiments in multiple types of cells and human lung models before observing the effects of blocking NSUN2 in mice.

We compared NSUN2-deficient mice with wild-type mice to see how the viruses act, Li said.

“Once we inhibited NSUN2, viral replication in the lung decreased and there was less pathology in the lung, and that correlated with enhanced type 1 interferon production.

This finding in mice and our other experiments proved that NSUN2 is a druggable target, Li added.

Udayavani is now on Telegram. Click here to join our channel and stay updated with the latest news.

Top News

Rajasthan-based Youtuber held for threatening to kill Salman Khan gets bail

Karnataka to remain driving force behind India’s GCC Industry: IT Minister Priyank Kharge

Heavy rainfall in DK, Udupi; DC declares holiday for schools, PU colleges on July 16

Geetha Tonse Pai of the Manipal Pai family passes away

No ‘good news’, for now enjoy ‘Bad Newz’: Vicky Kaushal on Katrina Kaif’s pregnancy rumours

Senior MLA Suresh Babu replaces Kumaraswamy as JD(S) leader in Karnataka Assembly

AI cameras installed in K’taka Assembly to record arrival, exit time of MLAs, duration of presence

Related Articles More

An overview on sarcomas – A diverse group of rare cancer

Raise a Toast: It’s World Rum Day!

Concerns arise about Zika virus spread in Karnataka

India’s population to peak in early 2060s to 1.7 billion before declining: UN

Case study highlights hidden health risks of prolonged exposure to pigeons


Dr. Rajkumar

Poisoning – Prevention

Mulbagal Dosa Vasavi Food Point

Donald Trump

Elephant attack

Latest Additions

Uproar in both houses of Karnataka legislature over Valmiki Corporation scam

Rajasthan-based Youtuber held for threatening to kill Salman Khan gets bail

Swati Maliwal assault : Delhi Police likely to file charge sheet on Tuesday

Karnataka to remain driving force behind India’s GCC Industry: IT Minister Priyank Kharge

TN CM condemns Karnataka over ‘non-release’ of Cauvery water, convenes all-party meet

Thanks for visiting Udayavani

You seem to have an Ad Blocker on.
To continue reading, please turn it off or whitelist Udayavani.