Swiss Study Reveals Shocking Role of SARS-CoV-2 Protein Nsp1 in Silently Destroying Human Genes!
Nikhil Prasad Fact checked by:Thailand Medical News Team Mar 28, 2025 3 weeks, 2 days, 11 hours, 7 minutes ago
Medical News: Scientists from the University of Bern in Switzerland have made a groundbreaking discovery about a little-known viral protein that could be key to how the coronavirus hijacks human cells. The research team, led by Dr. Evangelos D. Karousis and including Emilie Bäumlin, Dominic Andenmatten, Jonas Luginbühl, Aurélien Lalou, and Nino Schwaller, has uncovered that a specific protein made by the SARS-CoV-2 virus, known as Nsp1, doesn’t just stop human cells from making their own proteins - it also actively destroys the messages (mRNA) inside the cells that carry genetic instructions.
Swiss Study Reveals Shocking Role of SARS-CoV-2 Protein Nsp1 in Silently Destroying Human Genes!
Nsp1 is the very first protein made by the virus once it enters the body. This protein has a brutal job: it shuts down the host's protein production machinery so the virus can take over. But this
Medical News report uncovers an even more sinister twist. The researchers have now shown that Nsp1 also triggers the breakdown of the host's mRNA - the vital blueprints cells use to build proteins.
What’s especially alarming is that this destructive action by Nsp1 happens independently of its better-known role in blocking protein synthesis. Using a sophisticated cell-free system that mimics human cellular machinery, the scientists demonstrated that Nsp1 doesn’t need ongoing protein production or even ribosome collisions (which are signs of translation problems) to begin the mRNA destruction process. Just binding to the ribosome - the cell’s protein-making machine - is enough.
This research suggests a finely tuned mechanism by which SARS-CoV-2 ensures only its own genes get expressed. And in a comparative twist, the researchers also found that a related coronavirus, MERS-CoV, uses a version of Nsp1 that can block translation but does not cause mRNA destruction. This means that different coronaviruses have evolved distinct strategies to shut down human gene expression.
A Closer Look at Nsp1’s Deadly Functions
In healthy cells, mRNA acts as the courier of genetic information, carrying instructions from DNA to the cell's ribosomes to make proteins. When SARS-CoV-2 infects a cell, it makes Nsp1 almost immediately. This protein lodges itself into the ribosome's entry site, preventing the cell's own mRNAs from being read. The virus thus silences the cell's native functions and prepares it to become a virus factory.
The Bern team went a step further and showed that Nsp1 doesn’t just block mRNA from being read - it actually leads to its degradation. This means that the cell loses not only the ability to translate its mRNA but the messages themselves get deleted. The researchers observed that this degradation happens primarily at the beginning (5’ end) of the mRNA, an area critical for ribosome attachment.
Using precise mutations to the Nsp1 protein, the team was able to separate its two destructive functions. A mutant that couldn’t bind r
ibosomes failed to destroy mRNA. Another mutant, RK-AA, blocked translation but didn’t cause mRNA breakdown. This helped prove that mRNA degradation and translation inhibition are two distinct functions that can be uncoupled.
Even When Translation Stops Nsp1 Keeps Attacking
One of the most surprising findings was that Nsp1 could destroy mRNA even when translation was chemically halted. Researchers used compounds like puromycin and rocaglamide to stop protein production, but mRNA still degraded in the presence of active Nsp1. This proves that Nsp1 doesn’t rely on ribosomes being in the act of translation to do its damage.
They also showed that mRNAs without a protective cap - a chemical structure required for translation - were just as vulnerable. In other words, Nsp1 only needs to be present and attached to the ribosome to trigger destruction.
Protection of Viral Messages Suggests Co-Evolution
So why doesn’t the virus destroy its own messages? The answer lies in a clever evolutionary trick. The researchers demonstrated that viral mRNAs contain a specific structure in their 5’ untranslated regions (UTRs), especially a sequence known as SL1. This structure shields viral mRNAs from being degraded by Nsp1.
Each virus appears to have co-evolved its Nsp1 and SL1 structures to ensure self-preservation. SARS-CoV-2 Nsp1 will protect messages with a SARS-CoV-2 SL1, but not SL1s from MERS or bat coronaviruses. Likewise, MERS-CoV Nsp1 protects only its own viral messages.
This discovery shows that these viruses have customized their proteins and RNA structures to avoid self-destruction, a sophisticated level of viral adaptation.
Failed Attempts at Blocking Nsp1 Activity
The team also explored whether two drugs previously suggested as Nsp1 inhibitors - montelukast (an asthma medication) and ametantrone (an anticancer compound) - could prevent Nsp1 from shutting down host translation. Unfortunately, neither drug worked in their experiments. This suggests that finding a truly effective Nsp1 inhibitor remains a challenge.
Given the importance of Nsp1 in immune evasion and viral proliferation, it remains one of the most attractive targets for antiviral therapy. But drug developers will have to dig deeper to find compounds that can effectively block its actions.
Implications and Conclusions
This new study uncovers a chilling layer in the strategy of the SARS-CoV-2 virus. By showing that Nsp1 doesn’t merely inhibit the host's ability to make proteins but actually destroys the very messages used for that task, researchers have redefined how dangerous and invasive this viral protein truly is.
More disturbingly, this ability to decimate host mRNAs operates completely independently of protein synthesis or ribosomal activity, showing just how efficient Nsp1 is at neutralizing host defenses. This expands our understanding of how SARS-CoV-2 rapidly silences host responses like the interferon system - the body’s front-line defense against viral invaders.
Additionally, the fact that each coronavirus tailors its own Nsp1 and 5’ UTR partnership to avoid self-inflicted damage reveals an elegant viral evolutionary strategy. These partnerships ensure that while host messages are wiped out, viral messages are preserved and even favored in the translation machinery.
The failure of proposed inhibitors like montelukast and ametantrone to stop Nsp1 from executing its dual role is disappointing but also a vital reminder of the complexity involved in targeting viral proteins. Researchers will need to focus on disrupting the binding between Nsp1 and the 40S ribosomal subunit as a potential therapeutic route.
In conclusion, the SARS-CoV-2 Nsp1 protein is more than just a translation inhibitor - it is a precise molecular weapon that can dismantle the host's genetic messaging system. Future therapies that aim to counter this activity will be crucial in fighting not just COVID-19 but other related coronavirus infections.
The study findings were published in the peer reviewed journal: Cell Reports
https://www.sciencedirect.com/science/article/pii/S2211124725002591
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https://www.thailandmedical.news/news/study-finds-that-sars-cov-2-nsp1-protein-silences-host-genes-involved-in-antiviral-immune-responses
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