Nikhil Prasad Fact checked by:Thailand Medical News Team Sep 06, 2025 4 hours, 46 minutes ago
Medical News: How the Spike Protein Does More Than Just Enter Cells
Scientists have discovered that a small sequence in the SARS-CoV-2 spike protein, known as the RGD motif, plays a far more dangerous role than previously thought. Beyond allowing the virus to invade cells, this motif triggers powerful changes inside the body’s immune system. This
Medical News report reveals how it switches on harmful signals, weakens natural defenses, and may even worsen long COVID.
SARS-CoV-2 Spike Motif Triggers Dangerous Immune Shutdown
Research Institutions Behind the Breakthrough
The research was carried out by teams from the University of Sydney, the University of New South Wales, the Centenary Institute, the Westmead Institute for Medical Research, and Macquarie University in Australia. Their combined work sheds light on how one small part of the spike protein can cause widespread disruption.
The RGD Motif and TGF Beta Signaling
At the core of the findings is the RGD motif, located on the spike’s receptor-binding domain. This sequence interacts with integrins, proteins on cell surfaces that normally regulate attachment and communication. Once engaged, it sparks a chain reaction that activates TGF-β, a signaling molecule linked with fibrosis, inflammation, and immune suppression.
The study showed that when spike protein was present—whether in live virus, pseudoviruses, or as purified protein—it caused strong activation of TGF-β signaling. This led to the phosphorylation of SMAD3, a master regulator of gene expression, and a surge in production of PAI-1, a marker of tissue scarring.
Suppression of Interferons and Immune Defenses
One of the most alarming discoveries is that this same process suppresses interferon-β, a frontline antiviral signal. Normally, interferons alert surrounding cells to block viral replication. But under the influence of the spike RGD motif and TGF-β, this defense system is switched off, giving the virus a greater chance to spread. Laboratory experiments confirmed that blocking the RGD motif or inhibiting TGF-β prevented this immune shutdown.
Implications for COVID Severity and Long COVID
These findings suggest that the spike protein does more than allow entry into cells. It actively weakens immunity, promotes scarring, and prolongs damage. Persistent fragments of spike protein—detected in patients months after infection—may continue to drive TGF-β activity, fueling the long-term symptoms of long COVID. Drugs that block integrins or TGF-β are now being considered as potential treatments.
Study Conclusions
The researchers concluded that the RGD motif on the SARS-CoV-2 spike is not just a structural feature but a functional weapon of the virus. By activating TGF-β, it drives tissue damage and suppresses interferons, creating an environment where the virus can thrive and cause long-lasting harm. This deeper understanding highlights why COVID-19 can be so severe and why some patient
s continue to suffer long after the infection has cleared. Targeting this signaling pathway could open new doors for therapy, both in acute infections and in preventing the chronic complications of long COVID.
The study findings were published in the peer reviewed Journal of Virology.
https://journals.asm.org/doi/10.1128/jvi.00435-25
Thailand Medical News would to add that there is no difference between the spike proteins via natural infections or via the mRNA vaccines, they all have got the RGD motif. Viral persistence and the mRNA vaccine continual production of the spike proteins in the human body possibly imply that many are suffering from immune dysfunction or immunodeficiency issues.
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Medical News.
Read Also:
https://www.thailandmedical.news/news/breaking-medical-news-is-sars-cov-2-or-covid-19-vaccine-induced-immunodeficiency-behind-the-surge-of-meningitis-infections-in-france
https://www.thailandmedical.news/news/covid-19-drugs-tucaresol-emerging-as-a-potential-covid-19-antiviral-and-drug-to-treat-sars-cov-2-induced-lymphopenia-and-immunodeficiency
https://www.thailandmedical.news/news/deadly-immune-disorder-triggered-by-covid-19-infection-uncovered
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