Question

Before going in the cells, a coronavirus must first find a receptor protein on the cell’s carbohydrate layer. Design/Propose a simple experiment that prevents the virus entering into a cell. If coronavirus is already inside the cell, design an experiment to block it from forming varions.

Answer 1

Advances in the biology of coronaviruses have resulted in greater understanding of their capacity for adaptation to new environments, transspecies infection, and emergence of new diseases. New tools of cell and molecular biology have led to increased understanding of intracellular replication and viral cell biology, and the advent in the past five years of reverse genetic approaches to study coronaviruses has made it possible to begin to define the determinants of viral replication, transpecies adaptation, and human disease.

The coronavirus is named after the crownlike spikes that protrude from its surface. The virus is enveloped in a bubble of oily lipid molecules, which falls apart on contact with soap.

Entering a Vulnerable Cell

The virus enters the body through the nose, mouth or eyes, then attaches to cells in the airway that produce a protein called ACE2. The virus is believed to have originated in bats, where it may have attached to a similar protein.

Protective
wrapping

Viral RNA

Releasing Viral RNA

The virus infects the cell by fusing its oily membrane with the membrane of the cell. Once inside, the coronavirus releases a snippet of genetic material called RNA.

Viral protein

Viral RNA

Hijacking the Cell

The virus’s genome is less than 30,000 genetic “letters” long. (Ours is over 3 billion.) The infected cell reads the RNA and begins making proteins that will keep the immune system at bay and help assemble new copies of the virus.

Antibiotics kill bacteria and do not work against viruses. But researchers are testing antiviral drugs that might disrupt viral proteins and stop the infection.

Cell nucleus

Viral proteins

Making Viral Proteins

As the infection progresses, the machinery of the cell begins to churn out new spikes and other proteins that will form more copies of the coronavirus.

Assembling New Copies

New copies of the virus are assembled and carried to the outer edges of the cell.

Spreading the Infection

Each infected cell can release millions of copies of the virus before the cell finally breaks down and dies. The viruses may infect nearby cells, or end up in droplets that escape the lungs.

A Possible Vaccine

A future vaccine could help the body produce antibodies that target the SARS-CoV-2 virus and prevent it from infecting human cells. The flu vaccine works in a similar way, but antibodies generated from a flu vaccine do not protect against coronavirus.

How Soap Works

Soap destroys the virus when the water-shunning tails of the soap molecules wedge themselves into the lipid membrane and pry it apart.

The best way to avoid getting infected with the coronavirus is to wash your hands with soap, avoid touching your face, keep your distance from sick people and regularly clean frequently used surfaces.

Physical barriers to antibody

Before antibody can combine with and neutralize the virus, it must reach the site of virus replication. Barriers to the distribution of antibody include the cell membrane, which excludes antibody, and anatomic tissue barriers, which limit the distribution of macromolecules into certain organs such as the central nervous system.

Via cytotoxic cells

When a virus infects a person (host), it invades the cells of its host in order to survive and replicate. Once inside, the cells of the immune system cannot ‘see’ the virus and therefore do not know that the host cell is infected. To overcome this, cells employ a system that allows them to show other cells what is inside them – they use molecules called class I major histocompatibility complex proteins (or MHC class I, for short) to display pieces of protein from inside the cell upon the cell surface. If the cell is infected with a virus, these pieces of peptide will include fragments of proteins made by the virus.

A special cell of the immune system called a T cell circulates looking for infections. One type of T cell is called a cytotoxic T cell because it kills cells that are infected with viruses with toxic mediators. Cytotoxic T cells have specialised proteins on their surface that help them to recognise virally-infected cells. These proteins are called T cell receptors (TCRs). Each cytotoxic T cell has a TCR that can specifically recognise a particular antigenic peptide bound to an MHC molecule. If the T cell receptor detects a peptide from a virus, it warns its T cell of an infection. The T cell releases cytotoxic factors to kill the infected cell and, therefore, prevent survival of the invading virus (Figure 1).

Viruses are highly adaptable, and have developed ways to avoid detection by T cells. Some viruses stop MHC molecules from getting to the cell surface to display viral peptides. If this happens, the T cell doesn’t know there’s a virus inside the infected cell.

However, another immune cell specialises in killing cells that have a reduced number of MHC class I molecules on their surface – this cell is a natural killer cell or NK cell for short. When the NK cell finds a cell displaying fewer than normal MHC molecules it releases toxic substances, in a similar way to cytotoxic T cells, which kill the virally-infected cell.

Cytotoxic cells are armed with preformed mediators. Cytotoxic factors are stored inside compartments called granules, in both cytotoxic T cells and NK cells, until contact with an infected cell triggers their release. One of these mediators is perforin, a protein that can make pores in cell membranes; these pores allow entry of other factors into a target cell to facilitate destruction of the cell. Enzymes called granzymes are also stored in, and released from, the granules. Granzymes enter target cells through the holes made by perforin.

Once inside the target cell, they initiate a process known as programmed cell death or apoptosis, causing the target cell to die. Another released cytotoxic factor is granulysin, which directly attacks the outer membrane of the target cell, destroying it by lysis. Cytotoxic cells also newly synthesise and release other proteins, called cytokines, after making contact with infected cells. Cytokines include interferon-g and tumour necrosis factor-a, and transfer a signal from the T cell to the infected, or other neighbouring cells, to enhance the killing mechanisms.

Via interferons

Virally infected cells produce and release small proteins called interferons, which play a role in immune protection against viruses. Interferons prevent replication of viruses, by directly interfering with their ability to replicate within an infected cell. They also act as signalling molecules that allow infected cells to warn nearby cells of a viral presence – this signal makes neighbouring cells increase the numbers of MHC class I molecules upon their surfaces, so that T cells surveying the area can identify and eliminate the viral infection as described above.

Via antibodies

Viruses can also be removed from the body by antibodies before they get the chance to infect a cell. Antibodies are proteins that specifically recognise invading pathogens and bind (stick) to them. This binding serves many purposes in the eradication of the virus:

• Firstly, the antibodies neutralise the virus, meaning that it is no longer capable of infecting the host cell.
• Secondly, many antibodies can work together, causing virus particles to stick together in a process called agglutination. Agglutinated viruses make an easier target for immune cells than single viral particles.
• A third mechanism used by antibodies to eradicate viruses, is the activation of phagocytes. A virus-bound antibody binds to receptors, called Fc receptors, on the surface of phagocytic cells and triggers a mechanism known as phagocytosis, by which the cell engulfs and destroys the virus.
• Finally, antibodies can also activate the complement system, which opsonises and promotes phagocytosis of viruses. Complement can also damage the envelope (phospholipid bilayer) that is present on some types of virus