SARS-CoV-2 NSp2 Protein Found to Hijack Human Cell Pathways by Blocking Key Cellular Protein SmgGDS
Nikhil Prasad Fact checked by:Thailand Medical News Team Apr 22, 2025 1 hour, 31 minutes ago
Medical News: A groundbreaking new study from researchers at the Institute of Artificial Intelligence Biomedicine at Nanjing University and the Ministry of Education in China has revealed that the SARS-CoV-2 virus uses a specific non-structural protein, known as NSP2, to directly interfere with a vital human protein called SmgGDS. This newly discovered interaction sheds light on how the virus manipulates cellular machinery to aid its survival and spread.
SARS-CoV-2 NSp2 Protein Found to Hijack Human Cell Pathways by Blocking Key Cellular Protein SmgGDS
SmgGDS (short for Small G-protein dissociation stimulator) plays an important role in cell signaling and regulation. It acts as a guanine nucleotide exchange factor (GEF), which essentially helps “turn on” certain small proteins like RhoA and RhoC. These proteins are responsible for controlling important cellular behaviors such as movement, adhesion, and internal communication. This
Medical News report explains how SARS-CoV-2 hijacks this very system by binding its NSP2 protein directly to SmgGDS, effectively blocking it from doing its job.
What Is NSP2 and Why Is It Important?
NSP2 is one of the 16 non-structural proteins produced by SARS-CoV-2, the virus responsible for COVID-19. While the functions of many of these viral proteins are well understood, NSP2 has remained somewhat of a mystery until now. Previous research had shown that NSP2 is involved in regulating host cell metabolism, immune response, and energy transport. It also localizes to areas in infected cells known as double-membrane vesicles, which are involved in viral replication. But this new study has uncovered a previously unknown and highly specific role for NSP2. Using biochemical experiments and advanced protein analysis methods, the researchers found that SARS-CoV-2 NSP2 binds tightly to SmgGDS and inhibits its GEF activity. This means that NSP2 prevents SmgGDS from activating the small GTPase RhoA by blocking the necessary exchange of guanine nucleotides, essentially shutting down a crucial cellular signaling pathway.
How This Interaction Affects the Body
RhoA and its related GTPase proteins are critical for organizing the internal framework of cells. They play a role in how cells move, divide, and respond to external signals. By preventing SmgGDS from activating these proteins, SARS-CoV-2 may be sabotaging cellular defenses and promoting conditions favorable to its replication and survival.
More importantly, the study confirmed that this interaction between NSP2 and SmgGDS is unique to SARS-CoV-2. Similar proteins in other coronaviruses like SARS-CoV or MERS-CoV do not appear to bind SmgGDS. This specificity might explain why COVID-19 causes such a broad range of symptoms and has a unique impact on the human body, compared to earlier coronaviruses.
Structural Details Reveal Viral Strategy
The researchers were able to isolate both the full-length and truncated forms of the NSP2 protein using prokaryotic expression systems and confirm the interaction with SmgGD
S in lab experiments. Their data showed that the full-length NSP2 was required to maintain a strong interaction with SmgGDS, suggesting that the entire protein structure is essential for this viral strategy.
The study builds upon previous structural studies of NSP2, which showed that its N-terminal region includes three zinc finger domains, while the C-terminal region appears to be highly flexible and unstructured. Using AI-powered structural prediction tools like AlphaFold2, the researchers believe this flexible region may be what allows NSP2 to effectively latch onto host proteins like SmgGDS.
Broader Implications for COVID-19 and Future Treatments
The SmgGDS protein regulates many small GTPases beyond just RhoA, including those in the Ras and Rac families. These proteins control processes like cell growth, immune response, and even cancer progression. By blocking SmgGDS, SARS-CoV-2 could be disrupting a wide array of cellular systems, which might help explain the virus’s widespread effects on different organs and its role in triggering long COVID symptoms.
This discovery opens new doors for potential therapies. If drugs can be developed to protect SmgGDS from viral interference—or restore its activity once blocked—it may be possible to limit the virus’s ability to disrupt cellular functions and reduce disease severity. Furthermore, targeting this interaction could become a key strategy in fighting future strains or related viruses.
Conclusion
This important study provides new insights into how SARS-CoV-2 manipulates human cells by binding its NSP2 protein to a vital cellular regulator, SmgGDS. The virus’s ability to specifically block the GEF activity of SmgGDS and disrupt the function of small GTPases like RhoA may be a critical part of how it causes disease. Understanding this unique interaction not only expands our knowledge of viral pathogenesis but also offers new targets for therapeutic intervention. As the world continues to seek effective treatments and preventative strategies for COVID-19 and its long-term complications, discoveries like this highlight the complexity of the virus and the importance of continuing in-depth molecular research.
The study findings were published in the peer reviewed journal: Biochemical and Biophysical Research Communications.
https://www.sciencedirect.com/science/article/abs/pii/S0006291X2500542X
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