SARS-CoV-2 Spike Protein Interacts with Cytoskeletal Proteins, Potentially Disrupting Normal Cellular Functions
Nikhil Prasad Fact checked by:Thailand Medical News Team Jan 23, 2025 1 month, 1 day, 7 hours, 14 minutes ago
Medical News: Researchers from the Institut Systématique Évolution Biodiversité (ISYEB) at Sorbonne Université and the Université de Versailles Saint Quentin in France have uncovered intriguing insights into how the SARS-CoV-2 Spike (S) protein interacts with human proteins. Their study, aimed at understanding the intricate dynamics of viral infection, sheds light on potential mechanisms of viral entry and intracellular transport. This
Medical News report dives into the findings and their implications for future research and potential therapeutic interventions.
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SARS-CoV-2 Spike Protein Interacts with Cytoskeletal Proteins, Potentially Disrupting Normal Cellular Functions
Focus on the Spike Protein
The Spike (S) protein of SARS-CoV-2 is already known as the key that unlocks the host cell’s door by binding to the angiotensin-converting enzyme 2 (ACE2). However, researchers have now discovered that the Spike protein might target specific regions within human proteins - particularly coiled-coil regions in cytoskeletal and cytoskeleton-associated proteins. The cytoskeleton, an internal scaffold within cells, is integral to maintaining cellular shape, movement, and intracellular transport. Interference in this system can have significant implications for cell function, making this finding particularly noteworthy.
To arrive at their conclusions, the team reanalyzed the most comprehensive dataset of SARS-CoV-2 - human protein - protein interactions currently available. By focusing specifically on the Spike protein’s interactions, they revealed a significant overrepresentation of cytoskeletal proteins, particularly actin-binding proteins, among its partners.
Key Findings of the Study
The study identified 22 human proteins that interact with the SARS-CoV-2 Spike protein. Among these, 10 were actin-binding proteins, a statistically significant enrichment compared to their natural distribution in the human proteome. Actin-binding proteins play crucial roles in cell shape and intracellular transport - both essential for viral infection and replication.
Moreover, the research revealed that many of these Spike protein partners share structural similarities with the C-terminal region of the Myosin II heavy chain. Myosin II is a motor protein that interacts with actin filaments, contributing to muscle contraction, cellular motility, and intracellular transport. The C-terminal region of Myosin II is known for its coiled-coil structure, a motif that facilitates protein-protein interactions. This structural motif was identified in multiple cytoskeletal proteins interacting with the Spike protein.
Key proteins identified include:
-Myosin-9, Myosin-10, and Myosin-14: These cellular myosins play critical roles in intracellular transport and were confirmed as Spike interactors.
-Tropomyosins (alpha and beta chains): These proteins stabilize actin filaments, pro
tecting them from severing and facilitating cellular processes such as vesicle transport.
-Coronin-1C and Tropomodulin-3: Both are involved in stabilizing and bundling actin filaments, ensuring cellular integrity.
Interestingly, some of these proteins are linked to other essential cellular processes like mitosis and cilia or flagella movement, which may be co-opted by the virus to facilitate its spread within the host.
Cytoskeletal Manipulation by SARS-CoV-2
The cytoskeleton is a critical target for many viruses. It not only provides a structural framework but also facilitates the intracellular transport of viral components. By interacting with coiled-coil regions in cytoskeletal proteins, the SARS-CoV-2 Spike protein may disrupt these cellular processes to the virus’s advantage. For example:
-Intracellular Trafficking: Proteins such as kinesins and dyneins, which were also implicated in the study, are motor proteins that transport cargo along microtubules. Viruses may hijack these systems to reach replication sites within the host cell.
-Actin Filaments and Viral Entry: The dense network of actin filaments in cells could provide a pathway for viral particles to move to favorable entry points.
-Intermediate Filaments: While their role in viral infection is less understood, some intermediate filament proteins were found among the Spike protein interactors. For example, vimentin has been implicated in facilitating SARS-CoV-2 entry into human cells.
Potential Implications for Research and Treatment
The findings open new avenues for research into how the virus interacts with host cells. Therapeutic interventions targeting the coiled-coil regions of these cytoskeletal proteins could potentially disrupt the virus’s ability to hijack host cellular machinery.
Additionally, this study highlights the need for more detailed investigations into coiled-coil structures as potential targets for antiviral therapies. By focusing on these motifs, researchers could develop drugs that specifically block viral interactions with the host cytoskeleton without disrupting normal cellular functions.
Conclusions
This study provides compelling evidence that the SARS-CoV-2 Spike protein targets coiled-coil regions within cytoskeletal and cytoskeleton-associated proteins. These interactions likely play a pivotal role in viral entry and intracellular transport, crucial steps in the infection process. The statistical overrepresentation of actin-binding proteins and the shared structural motifs among these proteins underline the importance of the cytoskeleton in SARS-CoV-2 pathogenesis.
Importantly, the research emphasizes the potential for therapeutic strategies aimed at these interactions. By disrupting the virus’s ability to manipulate the cytoskeleton, it may be possible to develop treatments that hinder its ability to replicate and spread within the host. Further research is needed to validate these findings and explore their implications for other viral infections.
The study findings were published on a preprint server and are currently being peer reviewed.
https://www.biorxiv.org/content/10.1101/2025.01.20.633897v1
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https://www.thailandmedical.news/news/sars-cov-2-3clpro-main-protease-s-role-in-cytoskeletal-dynamics-and-stealth-intercellular-infection
https://www.thailandmedical.news/news/covid-19-news-p21-activated-kinase-1-pak1-mediated-cytoskeleton-rearrangement-facilitates-sars-cov-2-entry-and-ace2-autophagic-degradation
https://www.thailandmedical.news/articles/coronavirus
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