The lifecycle of SARS-CoV-2. Scientific version

Summary

The script delves into the intricate process of SARS-CoV-2 infection, highlighting how the virus targets ciliated cells in the airways. It details the virus's structure, with its spike protein playing a crucial role in binding to the ACE-2 receptor on host cells. The narrative unfolds the viral entry, hijacking of the host's translation machinery, and replication within double membrane vesicles. It concludes with the assembly of new viral particles and their release, leading to cell death and further infection, encapsulating the lifecycle of SARS-CoV-2.

Takeaways

• 🔬 The air we breathe in our airways interacts with various healthy respiratory cells, including ciliated cells that move mucus.
• 🦠 SARS-CoV-2 targets ciliated cells in the airways, using its spike protein to initiate infection.
• 🧬 The virus is composed of a simple structure with an outer membrane, spike, envelope, and membrane proteins, and a nucleocapsid protein assembly holding its RNA.
• 🔗 The spike protein's glycosylation helps it evade the immune system, and mutations in this protein can increase the virus's infectiousness.
• 🔒 The virus binds to the ACE-2 receptor on host cells, with the spike protein undergoing a series of cleavages to facilitate entry.
• 🌐 Once inside the cell, the viral RNA is translated into a chain of non-structural proteins (nsps) that take over the host's translation machinery.
• ✂️ Nsp3 is crucial for cleaving the protein chain, allowing the virus to hijack the cell and begin producing viral components.
• 🔄 The viral RNA translation is regulated by a pseudoknot, which affects the production of different nsps and the overall replication process.
• 🌐 The endoplasmic reticulum (ER) is altered by nsps to form double membrane vesicles (DMVs), providing a safe environment for viral replication.
• 📦 New viral particles are assembled with the help of nucleocapsid proteins packaging the viral RNA and other structural proteins forming on the ER.
• 🚀 Viral particles are released from the host cell through budding and cell lysis, spreading to infect neighboring cells and continuing the cycle.

Q & A

What are the main targets of the SARS-CoV-2 coronavirus in our airways?

The main targets of the SARS-CoV-2 coronavirus in our airways are the ciliated cells, which have hairlike structures called cilia that move mucus along.

What are the three types of proteins found on the outer membrane of the SARS-CoV-2 virus?

The three types of proteins found on the outer membrane of the SARS-CoV-2 virus are spike, envelope, and membrane proteins.

How does the spike protein of the SARS-CoV-2 virus initiate infection?

The spike protein of the SARS-CoV-2 virus initiates infection by binding to a receptor on the host cell called ACE-2.

What is the function of the glycosylation of the spike protein?

The glycosylation of the spike protein provides a coat of sugars that helps to hide the virus from the body's immune system.

What is the role of the S1 and S2 domains of the spike protein during the viral entry process?

The S1 domain of the spike protein is the outer part that binds to the host cell, and after binding, it is cut off by furin. The S2 domain, once freed, anchors into the host cell membrane, facilitating the fusion of the viral and host cell membranes.

How does the SARS-CoV-2 virus take over the host cell's translation machinery?

The SARS-CoV-2 virus takes over the host cell's translation machinery by using non-structural proteins (nsps) that are produced after the viral RNA is translated. These nsps prevent the ribosome from reading the host cell's mRNA, focusing its efforts on viral RNA.

What is the purpose of the double membrane vesicle (DMV) created by the virus in the host cell?

The double membrane vesicle (DMV) created by the virus in the host cell provides a safe, enclosed environment for the viral genome to be copied and for the production of new viral components.

How are the subgenomic mRNA strands used in the production of new viral particles?

Subgenomic mRNA strands are processed by the host cell to create the proteins that go onto the new viral particle, including spike, membrane, envelope, and nucleocapsid proteins.

What is the role of the nucleocapsid protein in the packaging of the viral genome?

The nucleocapsid protein packages the viral genome RNA into what will become the contents of the new viral particles, sitting by the DMV pore ready to grab onto the viral genome RNA as it exits the DMV.

How does the new viral particle bud off from the host cell?

The new viral particle buds off from the host cell when the membrane compartment containing the viral particles fuses with the outer cell membrane, releasing the viral particles.

What happens to the host cell after it has produced a large number of viral particles?

After producing a large number of viral particles, the host cell dies, releasing a wave of new virus particles into the surrounding tissue, which are ready to spread and infect nearby cells.