Understanding the Virus that Causes COVID-19, with Animation

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Coronaviruses are a large family of enveloped, RNA viruses. There are 4 groups of coronaviruses: alpha and beta, originated from bats and rodents; and gamma and delta, originated from avian species. Coronaviruses are responsible for a wide range of diseases in many animals, including livestock and pets. In humans, they were thought to cause mild, self-limiting respiratory infections until 2002, when a beta-coronavirus crossed species barriers from bats to a mammalian host, before jumping to humans, causing the Severe Acute Respiratory Syndrome, SARS, epidemic. More recently, another beta-coronavirus is responsible for the serious Middle East Respiratory Syndrome, MERS, started in 2012. The novel coronavirus responsible for the Coronavirus Disease 2019 pandemic, COVID-19, is also a beta-coronavirus. The genome of the virus is fully sequenced and appears to be most similar to a strain in bats, suggesting that it also originated from bats. The virus is also very similar to the SARS-coronavirus and is therefore named SARS-coronavirus 2, SARS-CoV 2. At the moment, it’s not yet clear if the virus jumped directly from bats to humans, or if there is a mammalian intermediate host.

Coronavirus genome is a large, single-stranded, positive-sense RNA molecule that contains all information necessary for the making of viral components. The RNA is coated with structural proteins, forming a complex known as nucleocapsid. The nucleocapsid is enclosed in an envelope, which is basically a LIPID membrane with embedded proteins. From the envelope, club-like spikes emanate, giving the appearance of a crown. This is where the “corona” name came from.

The integrity of the envelope is essential for viral infection, and is the Achilles’ heel of the virus, because the lipid membrane can easily be destroyed by lipid solvents such as detergents, alcohol and some disinfectants. In fact, enveloped viruses are the easiest to inactivate when they are outside a host.

In order to infect a host cell, the spikes of the virus must BIND to a molecule on the cell surface, called a receptor. The specificity of this binding explains why viruses are usually species specific – they have receptors in certain species, and not others. Host jumping is usually triggered by mutations in spike proteins which change them in a way that they now can bind to a receptor in a new species.

The novel coronavirus appears to use the same receptor as SARS-coronavirus for entry to human cells, and that receptor is the angiotensin-converting enzyme 2, ACE2. Infection usually starts with cells of the respiratory mucosa, then spreads to epithelial cells of alveoli in the lungs.

Receptor binding is followed by fusion of the viral membrane with host cell membrane, and the release of nucleocapsid into the cell. The virus then uses the host machinery to replicate, producing viral RNAs and proteins. These are then assembled into new viral particles, called virions, by budding into intracellular membranes. The new virions are released and the host cell dies.

Uncontrolled growth of the virus destroys respiratory tissues, producing symptoms. Infection triggers the body’s inflammatory response, which brings immune cells to the site to fight the virus. While inflammation is an important defense mechanism, it may become excessive and cause damage to the body’s own tissues, contributing to the severity of the disease. In an otherwise healthy person, there is a good chance that the virus is eventually eliminated and the patient recovers, although some may require supportive treatments. On the other hand, people with weakened immune system or underlying chronic diseases may progress to severe pneumonia or acute respiratory distress syndrome, which can be fatal.

 

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